This is an appeal against the revocation of the opposed patent.
Claim 1 as granted, which was identical to claim 1 of the sole request before the Board, read:
1. The use of raloxifene, or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for preventing or treating postmenopausal osteoporosis in a postmenopausal woman wherein said medicament is in the form of a tablet or capsule.
The Board had to examine whether this claim contravened A 100(c):
[2.1] Claim 1 of the main request is identical to claim 1 as granted. The assessment of the ground of opposition under A 100(c) is within the framework of the present appeal. In particular, the decision of the opposition division has to be reviewed also in relation to A 100(c), and [opponent 1] already submitted arguments pursuant to A 100(c) with its response to the grounds of appeal […].
[2.2] The patent in suit derives from European patent application 04101615.5, which was filed as a divisional application of European patent application 97200262.0 (parent application), published as EP-A-0781555. The parent application was filed as a divisional application of European patent application 93305860.4 (root application), published as EP-A-0594952. The documents concerning the description and examples as originally filed are identical for the three applications: root (GA), parent (PA) and its divisional (OA) (i.e. the application from which the patent in suit derives). However, the claims as originally filed in the root application (GA) are different from the claims as originally filed in the parent (which are the same as in its divisional application).
It is an undisputable fact that the set of claims of the application as originally filed (OA) does not contain any claim or combination of claims which corresponds to the use in claim 1 of the main request. As a matter of fact claims 1 to 8 of the application as originally filed (OA) related to a pharmaceutical unit dosage form comprising an amount of from 50 to 200 mg of a compound of formula I (generic compound class defined by means of a Markush formula). Moreover, none of the claims of the application as originally filed (OA) specified any medical indication. Thus, the claims of the application as originally filed do not provide any allowable basis under A 123(2) for claim 1 as granted.
Therefore, it has to be investigated whether the description and examples of the application as filed provide a basis for the subject-matter claimed in claim 1 of the main request. Such an investigation corresponds identically to the investigation of the basis in the root (GA) and parent (PA) applications, in view of the identical text of the description and examples.
[2.3] Claim 1 of the main request is a medical use claim in the Swiss-type form, which relates to the use of a single drug, namely raloxifene, which may also be in the form of a pharmaceutically acceptable salt. The particular use to which the drug has to be functionally linked concerns the specific medical indication of the prevention or treatment of postmenopausal osteoporosis, and the particular subgroup of patients is identified as “a postmenopausal woman”. As regards the form in which the medicament is to be administered, it is specified as a tablet or capsule. A body of jurisprudence of the technical boards of appeal identifies the technical elements which have been specified in claim 1 (e.g. identity of the drug, form of the medicament and/or mode of administration, medical indication concerning a disease or ailment, group of patients) as technical features which may confer novelty and/or inventive step on the subject-matter of a medical use claim in the Swiss-type form.
Therefore, it has to be assessed whether the application as originally filed singles out the “invention” specified in claim 1, and whether the claim includes technical information not directly and unambiguously derivable from the application documents as originally filed.
[2.4] The application as originally filed discloses a group of 2-phenyl-3-aroylbenzothiophenes in the prevention of bone loss […]. However, the prevention of bone loss is not a synonym for the prevention of postmenopausal osteoporosis in a postmenopausal woman. As stated on page 1, lines 7-11 of the application as originally filed: “The mechanism of bone loss is not well understood, but in practical effect, the disorder arises from an imbalance in the formation of new healthy bone and the resorption of old bone, skewed toward a net loss of bone tissue”. Claim 1 of the main request does not explicitly reflect the technical effect of “prevention of bone loss”.
Moreover, as stated in […] the application as originally filed, “Unchecked, bone loss can lead to osteoporosis, a major debilitating disease whose prominent feature is the loss of bone mass (decreased density and enlargement of bone spaces) without reduction in bone volume, producing porosity and fragility” (emphasis added). In other words, bone loss is not the only feature of osteoporosis, and thus the prevention of bone loss does not equate to the prevention of osteoporosis.
Further, [… in] the application as originally filed it is stated that: “The inhibition of bone loss contemplated by the present method includes both medical therapeutic and/or prophylactic treatment” (emphasis added). Therefore, this passage does not disclose the preventive treatment of postmenopausal osteoporosis in a postmenopausal woman (which may inter alia address secondary prevention of osteoporosis in an earlier stage of post-menopause, as well as tertiary prevention in a post-menopausal woman already suffering from advanced post-menopausal osteoporosis); it simply discloses the prophylactic treatment which is exclusively linked to the technical effect (not mentioned in claim 1) of inhibition of bone loss.
This understanding […] is in line with the following passage […] of the application as originally filed: “Thus, the current invention provides a method of inhibiting bone loss comprising administering to a human in need of treatment an amount of a compound of formula I that inhibits bone loss but does not significantly affect the primary sex target tissues” (emphasis added).
Moreover, […] “A significant feature of post-menopausal osteoporosis is the large and rapid loss of bone mass due to the cessation of estrogen production by the ovaries” (emphasis added). On the one hand there is a specific form of bone loss encountered in post-menopausal osteoporosis, which is not shared by each patient suffering from bone loss, and on the other hand bone loss is not the only feature of post-menopausal osteoporosis.
[2.5] Therefore, the application as originally filed discloses the technical effect of prevention of bone loss, which is not identical to the prevention of post-menopausal osteoporosis in a post-menopausal woman, as can be inferred from the following passage: “The benzothiophenes of formula I are able to antagonize classical estrogenic responses in primary sex target tissues without significantly reducing bone density when given to intact or estrogen treated animals, and they prevent bone loss in estrogen deficient animals. This dichotomy indicates selective agonist/antagonist actions on specific target cells which would appear to be highly desirable in treatment of menopausal syndrome” […] (emphasis added).
[2.6] In view of the analysis above, the application as originally filed does not specifically disclose the prevention of post-menopausal osteoporosis in a postmenopausal woman.
[2.7] Additionally, if taken in general terms, “Bone loss occurs in a wide range of subjects, including post-menopausal women, patients who have undergone hysterectomy, patients who are undergoing or have undergone long-term administration of corticosteroids, patients suffering from Cushing’s syndrome, and patients having gonadal dysgensis” […] (emphasis added). Therefore, post-menopausal women are selected from a list of several possible options for the patients to be treated.
Even considering that raloxifene is disclosed as the most preferred compound of formula I […], apart from the selection and individualisation of the disease to be treated and the subgroup of patients, a further selection has also taken place in claim 1 of the main request, namely that concerning the form of the medicament as a tablet or capsule. The application as originally filed discloses that the compounds of formula I can be formulated with common excipients, diluents or carriers, “and formed into tablets, capsules, suspensions, powders and the like” […]. “The compounds can also be formulated as elixirs or solutions for convenient oral administration or as solutions appropriate for parenteral administration, for instance by intramuscular, subcutaneous or intravenous routes” […].
Further, […] it is stated: “The particular dosage of a compound of formula I required to treat or inhibit bone loss according to this invention will depend upon the severity of the disease, its route of administration, and related factors that will be decided by the attending physician”. The application as originally filed does not single out tablets and capsules in connection with the prevention and treatment of post-menopausal osteoporosis in a post-menopausal woman. [… I]t is stated that “It is also advantageous to administer such a compound by the oral route to an aging human (e.g. a post-menopausal female or a male showing evidence of bone loss by X-ray analysis)” (emphasis added). First of all, the oral route does not equate with the selection of tablets and capsules since other forms such as solutions and suspensions may also be possible. Moreover, the patient is identified as an aging human and there is no preference for post-menopausal women to be linked to a particular dosage form. The previously cited passage […] of the application as originally filed ends with the following statement […]: “For such purposes the following oral dosage forms are available”. This is followed by a new section with the title “Formulations”, in which several specific examples are disclosed with the proviso that “in the formulations which follow, “Active ingredient” means a compound of formula I” […]. Formulations 2, 3 4 and 5 relate to specific “Raloxifene capsules” in which the raloxifene is in the form of raloxifene hydrochloride. The tablets of formulations 6 and 7 relate to “an active ingredient”, and table 1 on pages 21-22 lists raloxifene as free base and as hydrochloride salt (compounds 20 and 21). The capsules and tablets exemplified are not representative of any possible tablet or capsule containing raloxifene or a pharmaceutically acceptable salt thereof, but illustrate particular tablets and capsules. Additionally, suspensions are also exemplified […]. In the ovarectomized rat model for post-menopausal osteoporosis illustrated in example 1 of the application as originally filed, the rats are treated with raloxifene, administered as the hydrochloride […]. Even if in example 3 of the application as originally filed it is stated […] that raloxifene was administered orally to the ovarectomized rats, there is no basis in examples 1 or 3 for the choice of the form of the medicament as tablet or capsule. As regards example 5, raloxifene was administered as the hydrochloride […] to a particular subgroup of post-menopausal women, namely those aged 45-60, receiving oral capsule formulations […].
Summarising, the examples concerning formulations illustrate specific formulations where the drug is present as hydrochloride salt, or as free base, but do not allow a generalisation to any tablet or any capsule. As regards the examples which concern the animal model for the treatment of post-menopausal osteoporosis, they do not provide any basis for the choice of tablets and capsules as the preferred form of the medicament. Finally, example 5 exclusively concerns the administration of the hydrochloride salt in the form of capsules.
[2.8] Therefore, claim 1 includes technical information which is not directly and unambiguously derivable from the application as originally filed and singles out subject-matter which was not disclosed in an individualised manner in the application as originally filed (this analysis applies mutatis mutandis to the PA and the GA).
Consequently, the main request fails on grounds pursuant to A 100(c) since claim 1 extends beyond the content of the application as originally filed and the parent and root applications as originally filed.
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