EP 2 371 361 B1 relates to methods to mobilise progenitor/stem cells in subjects by administering certain polyamines.
Brief outline of the case
The patent was maintained by the OD according to AR6.
The proprietor and opponents 1, 2, 4, 5 and 6 (out of 7) each lodged an appeal against the OD’s decision.
In the requests admissibly on file, some claims were found to infringe Art 7(1), whereby claim 1 of AR 19-21 was lacking N over D13=WO 00/45814, cited as X in the ESR.
The board thus revoked the patent.
Claim 1 of AR 19
It was common ground that the subject-matter of claim 1 of AR 19 encompassed a substance, plerixafor, for use in a multi-step method characterised by the following steps:
– “step i”: administering plerixafor to a healthy stem-cell donor, to mobilise progenitor and/or stem cells in this donor (“step i)”),
– “step ii)”: harvesting said progenitor and/or stem cells via apheresis
– “step iii)”: using these cells in allogenic PSC transplantation
Plerixafor is an immunostimulant used to mobilise hematopoietic stem cells in cancer patients into the bloodstream. The stem cells are extracted from the blood and transplanted back to the patient.
The proprietor’s point of view
The proprietor contended that the mobilisation of the donor’s PSCs, i.e. the movement of the PSCs from the donor’s bone marrow to the donor’s peripheral blood, gave rise to the following therapeutically beneficial effects in healthy stem-cell donors.
- (i) Enhanced wound healing (see paragraph [0018] of the patent)
- (ii) Restoring organ tissue (see paragraph [0018] of the patent)
- (iii) Regeneration of myocardium (see paragraph [0037] of the patent)
- (iv) Increase in the level of circulating blood cells, giving rise to an improved ability to fight infection and increased oxygen transport
The proprietor contended that the process of harvesting PSCs may involve a number of separate apheresis sessions in order to collect sufficient cells, each process causing unpleasant side effects for the donor and being associated with the risk of serious complications.
Administering plerixafor in advance of cell collection would reduce the number of apheresis procedures needed to collect the required number of PSCs, and thereby reduce the side effects and complications.
The use of plerixafor also entirely avoided the need for collection of cells from the bone marrow, which was associated with serious side effects.
The proprietor further contended that the reduction in side effects and complications due to a reduced number of apheresis sessions represented a method for treatment by therapy in the context of Art 53(c).
The board’s decision
For the board it was relevant whether the method steps of such a multi-step method pertain “by their nature” to a method for treatment by therapy or surgery making use of the claimed compound.
If so, this therapeutic or surgical method constitutes the medical use possibly conferring novelty and inventive step to the claimed compound.
Hence, for such a claim to be considered as a purpose-limited product claim under Art 54(5), it is not sufficient
- (a) that the multi-step method as a whole is excluded from patent protection in accordance with Art 53(c) by virtue of only part of the method steps pertaining to a treatment of a human or animal body by therapy or surgery,
- (b) the individual steps of the multi-step method are causally linked to one another, and/or
- (c) the use of the claimed substance or composition in one method step facilitates one or more subsequent method steps.
In addition, the claimed substance or composition must have a treatment-related link to a medical step of the multi-step method in that the claimed substance or composition as such must exert a technical effect pertaining to a therapeutic or surgical step in the human or animal in which the at least one medical step is carried out, i.e. the claimed substance or composition must have activity in relation to therapy or surgery in this medical step.
The board held that each step of the multi-step method of claim 1 is to be considered separately to determine whether one step of this method (or more) is a medical step and, if so, whether plerixafor has activity in relation to surgery or therapy in this step.
Step i)
Step i) defines a method for treatment of a healthy stem-cell donor with plerixafor. The technical effect of this treatment is the mobilisation of the donor’s PSCs, i.e. the movement of the PSCs from the donor’s bone marrow to the donor’s peripheral blood.
The PSCs mobilised in step i) remain within the donor’s body for less than two days before being harvested and are not returned to it afterwards.
The board did not find it credible that the PSC donor treated in step i) will benefit from any of the effects listed by the proprietor.
The board therefore concluded that step i) of claim 1 did not define a method for treatment by therapy.
Step ii)
In step ii) of the multi-step method of claim 1, the PSCs mobilised in step i) are harvested via apheresis. Apheresis is a method in which blood is removed from a person, passed through an apparatus for separating and collecting a particular constituent of the blood (in the current case, PSCs), and re-transfused without the collected constituent
For the steps of removing and returning blood, cannulas are inserted into the person’s veins.
The technical effect of step ii) is the removal of the PSCs mobilised in step i) from the donor’s peripheral blood. Undisputedly, this effect pertains to a surgical step.
For the board, the reduction in side effects and complications is independent of the surgical step ii), i.e. the removal of the PSCs mobilised in step i) from the donor’s peripheral blood, which is done by the apheresis procedure alone.
The board held that plerixafor mobilises the product (PSC population) that is to be collected in a subsequent surgical step (apheresis), but it does not affect the surgical procedure itself, regardless of whether steps i) and ii) are considered as two separate steps or as one single surgical step.
The apheresis procedure defined in step ii) is carried out on healthy PSC donors who are not in need of this or any other type of PSC harvesting procedure to restore their health, nor do they require such a procedure to prevent a pathological condition that would otherwise arise.
The board therefore concluded that plerixafor did not exhibit any activity in relation to surgery or therapy in step ii), i.e. there is no treatment-related link between plerixafor and step ii).
Step iii)
Step iii) includes the transplantation of the PSCs harvested in step ii) into a subject other than the donor of these PSCs (allogeneic PSC transplantation).
It was common ground that this step has surgical character. The proprietor did not invoke any activity of plerixafor in relation to surgery in this step.
Step iii) gives rise to a therapeutic effect in the recipient of the PSC transplant. Step iii) thus additionally defines a method for treatment by therapy.
However, the therapeutic effect in step iii) results from the donor’s PSCs collected in step ii), not from plerixafor. It is accepted that plerixafor is essential for these PSCs. Plerixafor not only achieves a clinically relevant number of these PSCs in the bloodstream, but also appears to mobilise the right type of PSCs to enable effective haematological reconstitution.
There is no treatment-related link between plerixafor and the therapeutic effect achieved in step iii) via plerixafor’s PSC mobilisation activity in step i). These two technical effects occur in distinct, non-overlapping groups of subjects, i.e. healthy PSC donors versus patients in need of a PSC transplant.
Moreover, step iii) is not necessarily closely associated with the preceding steps i) and ii) in terms of time as claim 1 is silent on this point. .
The board concluded that plerixafor does not have any activity in relation to surgery or therapy in step iii), i.e. there is no treatment-related link between plerixafor and step iii).
The overall conclusion of the board was that the multi-step method of claim 1 comprises two medical steps, i.e. steps ii) and iii); however, the claimed compound (plerixafor) does not have any activity in relation to surgery or therapy in either of these two steps.
As a consequence, claim 1 is not a purpose-limited product claim under Arti 54(5). Instead, claim 1 is to be understood as being directed to a compound, plerixafor, suitable for use in the multi-step method of claim 1.
Claim 1 of AR 19-21 was therefore lacking N over D13=WO 00/45814.
Comments
The case is interesting in that it makes clear that in spite of a method comprising medical steps under Art 53(c), the product used in such a method is not automatically benefiting from the provisions of Art 54(5).
A product, here the plerixafor, might improve harvesting specific cells from healthy donors, but if it is not, as such, linked with any therapeutic effect, it will lack N if this product is known in spite of being used in a multistep medical method.
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