On 6. More 2014 had the 3. Senate of the Federal Patent Court on an appeal ratiopharm GmbH against the supplementary protection certificate EN 199 75 011 MSD Oss B.V. (Netherlands) to decide. The Protection Certificate relates to the progestin desogestrel, the so-called as the sole agent in the. "Mini-pill" is included, marketed by MSD under the trademark "Cerazette". The protection certificate was invalid.
CERTIFICATE:
3 Ni 21/12
Bundespatentgericht 3 Ni 21/12 JUDGMENT by 6. More 2014
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The patent invalidity thing
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concerning the supplementary protection certificate EN 199 75 011
has 3. Senate (Nullity Senate) the Federal Patent Court on the basis of the hearing on 6. More 2014 composed by the presiding judge Schramm, the judge Guth, Judges Dipl.-Chem. Dr. Proksch Single Judge and the Dipl.-Chem. Dr. Gerster and Dipl.-Chem. Dr. Recognized hunters' rights:
I. The SPC DE 199 75 011 annulled.
II. The defendant shall pay the costs of the proceedings.
III. The verdict is against security in the amount of 120 % the amount to be enforced provisionally enforceable.
Facts
The action is directed against the order of 29. October 2004 of Dt-pean Patent- and Trademark Office for a period up to the 12. December 2012 for the active ingredient desogestrel granted supplementary protection certificate EN 199 75 011. This protection certificate is the most 12. December 1991 pending before the European Patent Office Pa, the priority of the European patent application 9020 3371 from 17. December 1990 be claimed, with effect for the FEDERAL-publicized Germany granted European Patent EP 0 491 443 B1 (Basic patent) underlying, which the German Patent- and Trademark Office under number DE 691 17 902 is performed and the duration of protection at 13. December 2011 ab-run is. Against the applicant was title a temporary injunction proceedings on-
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reason of dispute certificate before the OLG Dusseldorf pending and damage compensation Rate- and infringement actions are in the room.
The basic patent is "the only progestogen contraceptive” and includes the Federal Republic of Germany nine claims, of which the An-claims 1, 5, 6, 7 and 8 are juxtaposed. The claims in suit of loud-tents in the German translation:
1. Combination and contraceptive kit comprising sequential daily dosage units for oral administration, each of which as the only effective contraceptive Be an integral part 70 to 80 Micrograms desogestrel, 3-Contains ketodesogestrel or mixtures thereof.
2. Combination and contraceptive kit according to claim- 1, wherein this pack 21 to 35 contains this daily sequen-tial dose units.
3. Combination and contraceptive kit according to claim- 2, wherein said gestodene is 3-keto-desogestrel, in the egg-lot ', from 75 Micrograms per dose unit is available.
4. Combination and contraceptive kit according to claim- 2, where this is gestodene, desogestrel, in an amount of 75 Micrograms per dose unit is available.
5. Application of a daily oral dosage unit, consisting essentially of 70 to 80 Micrograms of gestodene, which consists of the group of Gestodenen of desogestrel, 3-Ketodesogestrel or mixtures thereof, in the manufacture of a drug delivery system, said Arzneiab-display system being characterized in, that it consists of daily
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Dosage units consists, containing only a Gestodenverbindung as a therapeutically active ingredient-Zigen.
6. Drug delivery system comprising a package, the 26 to 30 containing sequential daily dosage units, consisting essentially of 70 to 80 Consist micrograms of a compound, which consists of the group of desogestrel, 3-Ketodesogestrel and mixtures thereof.
7. Contraceptive kit of the type, includes the daily dose of progestogen-only units, wherein the improvement the An-use of 70 to 80 Micrograms of 3-keto-desogestrel, Includes Desoge-strel or mixtures thereof as the progestogen in these daily dosage units.
8. Process for the preparation of a drug delivery system, comprehensive: Mixing predetermined quantities of a progestogen, selected from the group consisting of desogestrel, 3-Ketodesoge-strel and mixtures thereof, with predetermined quantities of excipients and converting the mixture into Dosisein-units, each of which 70 to 80 μg Desogestrel, 3-Ketodesoge-strel or contains mixtures thereof, and packaging multiple number of dosage units in a pack.
9. The method of claim 9, wherein said mixture is converted into dosage units, selected from the group consisting of capsules and tablets. "
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The applicant relies on the following documents:
NiK1 EP 0 491 443 B1
NiK2 Cullberg, G. et al., Acta Obstet. Gynecol. Scand. Suppl., 1982, 111, S. 21 to 28
NiK3 Viinikainen, The. et al., Acta Endocrinologica, 1976, 83, S. 429 to 438
NiK4 Viinikainen, The. et al., Contraception, 1977, 16, S. 51 to 58
NiK5 Short appraisal of the EP 0 491 443 B1 of Prof. Dr. H. Kuhl from
6. June 2012
NiK6 Short appraisal of the EP 0 491 443 B1 of Prof. Dr. H. The. Summer from 26. More 2012
NiK7 Declaration Hermann von Jan Tijmen Coelingh Bennink, PhD, in the grant procedure to US 5,461,041 (Application Number 08/183,644) from 27. February 1995
NiK8 decision to grant the German Patent- and Trademark Office for the Protection Certificate EN 199 75 011 from 29. October 2004
NiK9 Red List 1993, Edition Cantor Aulendorf / Wuertt.: Entries “Lo-velle®” and “Marvelon®”
NiK10 excerpt from the DIMDI database AMIS to “Notch” from
20. March 2012
NiK11 excerpt from the DIMDI database AMIS to “Marvelon” from
20. March 2012
NiK12 judgment of the European Court of Justice in Case C-322/10 of 24 November 2011 (Medeva) in German and English
NiK13 judgment of the European Court of Justice in Case C-422/10 of 24 November 2011 (Georgetown University) in German and English
NiK14 Expert Statement of Professor Dr. H. Kuhl from
14. June 2013
NiK15 DE 23 61 120 C2
NiK16 Information for Professionals “Yvette-ratiopharm®”, More 2012
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NiK17 ruling from the Oberlandesgericht Dusseldorf on appeal I-2 U 94/12 from 7. November 2013
Plant 1 Judgment of the District Court of Dusseldorf from 15 November 2012,
Yeah: 4The b 123/12
It claims, the dispute certificate is in accordance with Article. 15 Abs. 1 BUCHST. c) Regulation (EG) No.. 469/2009 of the European Parliament and of the Council of 6. More 2009 concerning the supplementary protection certificate for medicinal products in conjunction with § 16a and § 81 To explain the Patents Act to be void, because after the expiry of the basic patents were available grounds for invalidity, the nullity of the basic patent, in particular-special for lack of inventive step having regard to NiK2 in conjunction with NiK4, would have justified.
Furthermore, the protection certificate was contrary to the provisions of Article 3 Regulation (EG) No.. 469/2009 issued, because the authorization to place the product on traffic-desogestrel as pharmaceuticals in Germany, due to which the grant was made, was not the first authorization to place the product on Inver-traffic desogestrel as pharmaceuticals in Germany turned-sen, because this drug is in combination with the drug Ethi-nylestradiol in the contraceptives "Lovelle®" and "Marvelon®" prior to the approval of the certificate the dispute underlying drug Cerazette approved for the German market and have been in the trade.
The applicant seeks,
the supplementary protection certificate EN 199 75 011 for void-he cleared.
The defendant,
dismiss the action,
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and bases its argument on the following documents:
B1 judgment of the District Court of Dusseldorf from 15. November 2012, Yeah: 4The b 123/12
B2 judgment of the District Court of Dusseldorf from 15. November 2012, Yeah: 4The b 139/12
B3 “The pill with ethinylestradiol”, Expression of www.femaleaffaires.de
B4 “Mini Pill”, Expression of www.femaleaffaires.de
B5 “The estrogen-free pill ", Expression of www.femaleaffaires.de
B6 copy of the affidavit of Professor. Dr. Herjan J.T. Coelingh Bennink vom 7. September 2012
B7 leaflet to "Cerazette® 75 Microgram tablets "of December 2011
B8 judgment of the European Court of Justice in Case C-130/11 (Neurim) from 19. July 2012
B9 opinion of Dr. Helenius J. Kloosterboer vom 10. More 2013
B10 German translation of the report B9
B11 Cullberg, G. et al., Acta Obstet Gynecol Scand Suppl., 1982, 111,
S. 13 to 19
B12 opinion of Dr. Helenius J. Kloosterboer vom 29. August 2013
with 6 Facilities,
Plant 6: Rinehart, W., Popul. Rep. A. 1975, S. A-53 to A-67
B13 German translation of the report B12
B14 opinion of Dr. Helenius J. Kloosterboer vom 5. March 2014
B15 German translation of the report B14
B16 „Marvelon® – Product Monograph“, N. In. Organon, The Netherlands, 2000
The defendant disputes the applicant's arguments in full screen. The prior art, the development of conventional combina-onspräparate concerned primarily, in which the inhibition of ovulation is paramount and, give to those skilled in no stimulation, a desogestrel-containing Mo-
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provide nopräparat with this effect. Because at HRT of the prior art, the ovulatory activity play only a ne-bengeordnete role. The patentability of the patent dispute modern drug be-calm addition to its surprising advantages compared to already be-known monopreparations.
The impugned protection certificate is not in the manner of. 15 Abs. 1 BUCHST. a) Regulation (EG) No.. 469/209 void, because it does not handle itself containing in by the applicant ge-called authorizations for desogestrel drug compositions for admission for drug desogestrel as sole active ingredient of a product.
Reasons for the Decision
The action is in accordance. Art. 15 Abs. 2 and type. 3 Regulation (EG) No.. 429/2009 i. In. m. § 81 Patent Act allowed. The Verletzungs- threaten and damage claims due to the extinct dispute certificate to the applicant, is the neces sary-need for legal protection given.
The action is also well founded, because the patent in suit lying the dispute certificate to have basically precluded grounds for invalidity (Art. 15 Abs. 1 BUCHST. c) Regulation (EG) No.. 469/2009, in conjunction with § 16a and § 81 Patgan).
I.
1. The patent EP 0 491 443 B1 (= Basic patent) relates to preparations for contraception, a particular administration regime for RECEIVER-ception, the sole administration of desogestrel, 3-Ketodesogestrel or mixtures thereof comprising (vgl. Streitpatent NiK1 S. 2 Sp. 1 From. 3 to 6).
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a) The active ingredient desogestrel
is a gestagen (= Progestagen, referred to in the German translation of the patent dispute with gestodene) the 3. Generation and a derivative of the Nortestoste-ron, a naturally occurring sex. In the body is desogestrel – which is therefore a more prohormone – the actual drug, the 3-keto-desogestrel (= Etonogestrel)
converted (vgl. NiK3 S. 437 From. 9 to 13 and NiK5 S. 2 Abs. 7).
b) At the priority date of the patent was – as initially font is made with reference to various state of the art - known, that women of childbearing age by the administration of a progestogen contraception can be achieved. Thus, for example, would in the French-sian Patent Application No.. 2 223 018 and in U.S. Patent 3 822 355 described the authoriza-submission of sections increasing doses of a progestogen to RECEIVER-ception with a drug-free interval. Furthermore, it is a method of contraception in US Patent 4 018 919 and the bel-cal patent 773 064 known, in which two different progestogens, such. B. Norethindrone and Chlormadionacetat, would be administered. The other was in the US-
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Patent 4 171 358 described a method of contraception, in which a progestagen, such. B. Chlormadionacetat, from 6. to 16. Day of Menstruati-onszyklus'll administered, followed by a hormone-free interval. Comparison-face method would give the German Patent DT 1 950 857 and DT 1 965 881 an. Referring to other publications is also stated, that “progestogen-only”-Pills (= Single-drug or. The mini-pill) especially for breastfeeding, for older women or for women, in which estrogens are cont-raindiziert, which have a high blood pressure or where occur under administration of hormone combination products migraine or headache, be suitable. However, it should – despite the description of various "only Gesta-gen" -Verabreichungsregime – taking progestin-only HRT associated with an incomplete inhibition of ovulation and a relatively high failure rate. Therefore, it was proposed, the daily dose of progestin to he-heights, in order to achieve a complete Ovulationsinhibierung. A Dosiserhö-hung, however, have led to more frequent bleeding between periods. With the sole administration of progestins for contraception also a he-höhtes occurrence was observed by functional ovarian cysts, that formed after discontinuation of the mono preparation back (vgl. NiK1 Sp. 1 From. 7 to column. 2 From. 17).
2. Against this background, the patent in suit, the objective technical problem underlying, a "progestin-only" regime to provide -Verabreichungs RECEIVER-ception, which inhibits ovulation effectively, but does not lead to more frequent irregular bleeding or persistent ovarian cysts functional as with already known progestin HRT (vgl. NiK1 Sp. 2 From. 18 to 21).
3. This object is achieved according to claim 1 by a
1. Combination and contraceptive kit comprising sequential daily dosage units for oral adminis-chung,
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2. each of them as the only contraceptive active ingredient
2.a. Desogestrel, 3-Ketodesogestrel or mixtures thereof ent-keeping and
2.b. wherein the unit dose 70 to 80 Microgram amounts.
The object is achieved according to patent claim 5 further achieved by the use of a daily oral dosage unit consisting essentially of 70 to 80 Micrograms desogestrel, 3-Ketodesogestrel or mixtures as single thera-peutic active ingredient in the manufacture of a drug delivery system.
In addition, they will be solved according to patent claim 6 by a Arzneiabgabesys-tem, according to patent claim 7 by a contraceptive kit according to claim and 8 by a method for producing a drug-ABGA-besystems.
4. In those skilled in the present case it is a competent team, belong to any event, a scientific working gynecologist and a pharmaceuti-cal technologist.
II.
The SPC DE 199 75 011 turns out to be not bestandsfä-hig, because the claims 1 to 9 according expired basic patent EP 0 491 443 B1 would not have been quite stable for lack of patentability.
1. The claim 1 falls prey to the Cancellation, because the provision of a combination and contraceptive kit according to claim 1, comprises the sequential daily dosage units for oral administration, as
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contraceptive single active ingredient 70 to 80 Micrograms De-sogestrel, 3-Contain ketodesogestrel or mixtures thereof, no inventive step-cal intervention required.
1.1. The excitation, to take to resolve the underlying the patent in suit is based on task-desogestrel considered, received the expert with the know-tific publications NiK2 to NiK4. This is the person skilled in, who is dealing with the present problem, include in its deliberations, for he knows not only the most important publications in his field; he will first deal with these, to get an overview of the For-standing research in the field to be processed by him. He will direct his focus first on those particular substances, their arz-neiliche effect already the subject of scientific studies have been and have proven themselves if necessary at the relevant time as part of a kommerzi-ellen product on the same therapeutic area.
Accordingly, the skilled person on the priority date is the progestin desogestrel as part of the combined preparation “Marvelon®” (vgl. B16 S. 4 Abs. 1) as well known as in clinical studies. Looking for a progestin, the disadvantages outlined above previous contain a progestin-monotherapy components could be overcome, was due to the close-lying, to look on this hitherto not been used in accordance with progestin. This is particularly true reason, because the experts - such. B. As can be seen the light of scientific publication NiK4 – Desogestrel as one of the most effective progestins among the previously known progestogens, whose income is also not associated with the occurrence of adverse events, panelist (vgl. NiK4 S. 52 Abs. 1 i. In. m. the quote mentioned there (2) = NiK3 S. 430 Abs. 2 the. Set and S. 437 Abs. 3 and NiK 4 S. 56 Abs. 3 the. Set ). This conclusion is based on results, which were obtained with the first clinical trials. As part of this was laid-made, that it is desogestrel (= Org 2969) a progestin with very high ovulation-inhibiting effect, namely an inhibiting effect
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from 100 %, and this effect is in any case with a daily intake of 0,125 and 0,060 mg is obtained (vgl. NiK4 S. 52 Abs. 1 Set 4 and S. 56 Abs. 3 Set 2 i. In. m. the quote mentioned there (2) = NiK3 S. 429 Title and S. 436 Abs. 1 and B16 S. 12 „Inhibition of ovulation“ Abs. 1). As the building on this He-knowledge, described in the publication NiK4 further further sub-studies showed, was even with a daily dose of 0,030 All three women in this group determine Mil-ligramm suppression of ovulation, as well as five out of six participants of the group, the daily 0,015 income mg (vgl. S. 51 “Abstract”, S. 52 Abs. 1 Set 4 and 5 and S. 56 Abs. 3 Set 1). Compared with other already known progestins such as norethindrone, Chlormadinone, Lynestrenol or norgestrel, at the Dosierun gene of 0,300 or. 0,500 mg or. 0,050 to 0,075 mg only to Hem-determination of ovulation by 70 %, 77 %, 0 to 69 %, 85 to 91 % or 48 to 66 % lead (vgl. S. 56 Abs. 3), desogestrel proved not only as effective at significantly lower doses, but also as a gestagen, in the resulting counter-rate to these in a complete inhibition of ovulation. However, since in four of nine study participants were irregular bleeding between periods occurred, the authors of the publication NiK4 suggested conducting further clinical studies specifically for the active ingredient desogestrel alone or in combination with an estrogen-Kom (vgl. S. 57 Abs. 1 i. In. m. S. 52 Abs. 2).
Studies with the active ingredient desogestrel alone are in the 1982 published scientific articles NiK2 described, which in connection with a daily intake of 15 to 60 μg (= 0,015 to 0,060 mg) Concerns to be desogestrel-border care central and peripheral effects. The aim of this study was not only to determine the lowest dose for desogestrel, which leads to an inhibition of ovulation, but in particular also its effect on the cervix – and thus on the cervical mucus - as well as on the uterine mucosa, the endometrium. The investigations were carried out with ei-ner daily dosage of 15, 30 or 60 μg (vgl. S. 21 to. Sp. "Abstract" and re. Sp. Abs. 1). Regarding the ovulation-inhibiting effect was also evident in this study, that in any event, with a dose of 60 ug is achieved – He is a-
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result, the former with the results of studies – in. a. those described in the documents NiK3 and NiK4 – consistent (S. 26 re. Sp. Abs. 5 “Treatment cycle with 60 μg Desogestrel” and S. 27 to. Sp. “Ovulation inhibition by desoge-shot” and S. 28 to. Sp. Abs. 2). Moreover, it was with the use of de-sogestrel an increase in the viscosity of the cervical mucus are observed – a property, which also plays a role in the context of the fertile-contraceptive effect of progestogens. This change in consistency, the u. a. leads to decreased permeability of the cervical mucus for sperm, corresponded to the observed with the administration of other Progesterone (vgl. S. 27 re. Sp. ” Effects on cervical mucus”). Also, the effect on the endometrium of desogestrel, with the implantation of the egg is prevented, resembled that of other progestogens. It is an effect, when it is ver-probably – such as running the authors of the article NiK4 – one of the most important in relation to the contraceptive effect of continuous “Progestogen-only”-Should act treatment (vgl. S. 27 re. Sp. “Effects on the endometrium”). Side effects of clinical significance were not beo-bachtet, except spotting in half of the study participants, the 30 income micrograms desogestrel, while, in contrast to the participant, the daily 60 took micrograms of the drug, occurred no bleeding between periods (vgl. S. 26 split-border sales and re. Sp. Abs. 5 and S. 28 left Sp. Abs. 2).
Given this state of play needed no considerations innovative style, to bring to solving the present problem desogestrel as active ingredient a mono preparation for contraception into consideration. Thus, based on the publication NiK4 be seen, that the administration of the active ingredient desogestrel as monopreparation to their publication date already in view of the expert was (vgl. S. 57 Abs. 1). The conduct of such studies is-then described in scientific articles NiK2, where in the first movement to a continuous review article for, low-dose progestin-taking contraceptive Reference is made and is subsequently referred to as highly potent progestin desogestrel (vgl. S. 21 to. Sp. Abs. 1). The skilled artisan will motivation for these studies as well therefore in the
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See objective, provide a single preparation of desogestrel, because Ge subject of the research described in this article are those factors, which had been observed by experts to be essential for the effect of a "progestogen-only" -Präparates (vgl. Plant 6 to report B12, S. A-55 left / right column cross section) and these studies the excellent suitability of desogestrel alone for contraception and the low risk for the occurrence of adverse events confirmed or. was detected (vgl. NiK2 S. 21 „Abstract“, and S. 28 to. Sp. Abs. 2). The view, Mono preparation that the focus of the document NiK2 in the development of a Desoge-containing strel is, is even more to, as in co-hang is quoted discussing the effect of desogestrel on the endometrium to-the only one publication, the rates associated with taking this action-substance endometrial changes in terms of a continuous "progestogen-only" treatment (vgl. S. 21 to. Sp. the. Abs. and S. 27 re. Sp. Abs. 3). Looking for a Verabreichungs re-gime for contraception, which inhibits ovulation effectively, but does not lead to more frequent irregular bleeding or persistent functional Ova rialzysten as with already known progestin HRT, it was natural therefore, the given to the scientific article NiK2 excitation aufzu-access. Because the judge assigned to the task at hand skill in the art could reasonably be-given the study results described in the documents NiK4 and NiK2 from the start of it, that with the use of low dosages of desogestrel in the ovulation 100 % is inhibited and thus a counter-acting zeptiv monopreparation is provided, include those which the progestin-only HRT is superior, which are already used in the present case in question ste-existing disease area (see NiK4 S. 56 Abs. 3). This also is why, because the expert could also expect, that the A-acceptance is not connected to other undesirable side effects, after-the particular in connection with in connection with the administration of mini pills always expected metrorrhagia not about than usual recog-known addition, continuous, higher incidence was observed (vgl. NiK2 S. 21 „Abstract“ Abs. 3 Set 4 and 5 and S. 28 Abs. 2 le set).
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After it was thus obvious, appropriate to consider the use of desogestrel as the solu-tion of the patent in suit underlying problem in Recital, can also measure the, the active ingredient in a range from 70 to 80 micrograms to dose, not justify the inventive step. For the skilled person was - as stated above - known, that with a dose amount of 60 ug and 125 micrograms desogestrel an inhibition of ovulation 100 % is achieved (vgl. NiK4 S. 56 Abs. 3 and NiK2 S. 28 Abs. 2). Assuming he could determine the optimal dosage range for its objective then within the area bounded by these dosages range readily, d. h. those dose range, within which the desired contraceptive effect is observed with minimal side effects. The determination of this area but is based on dose-finding studies, attributable to the routine activities of the professional and require the application of any considerations innovative style.
This thus formulated monopreparations then packed in a contraceptive kit comprising sequential daily dosage units for oral administration to provide, corresponds to the generally accepted Dar-administration form of contraceptive, orally-active drugs. Therefore, this measure is not suitable, to contribute to the creation of inventive step.
The law raised by the dispute patentee advantageous intrinsic properties of desogestrel, as a new mechanism of action, a longer-Einnah mefenster or. a lower incidence of irregular bleeding between periods and persistent cysts, can lead to a different conclusion. Because they are merely the inevitable consequence of a - as stated above – close down action (vgl. BGH 2003, 317 Ls., 320 II.2.d)bb) – Cosmetic sunscreens). Moreover, it is apparent, how these will actually be achieved in practice, after - as indicated by the prescribing information for preparation "Yvette-ratiopharm” the applicant (= NK 16), the only active substance
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75 contains micrograms desogestrel, be seen - even a desogestrel-containing mono-preparation up to 50 % of women leads to irregular menstrual cycles (vgl. NiK16 S. 3 “4.8 Side effects”).
1.2. The contested claim 1 further comprising as an alternative Ausführungsfor-men said there dosage unit such, containing a single conception contraceptive-part 3-keto-desogestrel or mixtures of desogestrel and 3-keto-desogestrel. These stipulations may also not contribute to the creation of inventive step. The active ingredient 3-Ketode-sogestrel it is - as stated above – to the drug actually in Kör-per active. This was known to those skilled in the relevant time-point (vgl. Panic 3 S. 437 Abs. 1/the. 3 Phrases). This differs from the disputed claim 1 included only in dosage units, that in one case the prohormone, included in the other case, the actually acting hormone. The expert was able to go out due to its a priori which, that respectively with the use of 3-ketodesogestrel. Mixtures of desogestrel and 3-keto-desogestrel, the present problem can be solved in the same way with the desired success as with desogestrel. Therefore, the above reasoning applies equally to here.
1.3. To a different conclusion, the argument of the defendant füh-ren, the publications NiK2 to NiK4 would give to those skilled no evidence, De-sogestrel formulated as “Progestogen-only”-Provide preparation, because the emphasis was on the inhibition of ovulation. Because the skilled artisan recognizes namely, that these publications may be directed only to the development of a combina-onspräparates, there are important for monopreparations other factors, especially as the thickening of the cervical mucus.
Contrary to this view, the patentee dispute concerning the publication-tions NiK3 and NiK4 general studies of contraceptive action-ness of the active ingredient desogestrel se. Because none of these documents is the detected with desogestrel effect in terms of a simultaneous
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Gift with an estrogen, as it is done with the use of a Kombinationspräpa-rates, discussed. In contrast, the scientific articles NiK2 Mono preparation recognizable on the development of a desogestrel-containing contraception is directed to Emp.
With the studies according to the publication NiK3 both the ability of the progestin to inhibit ovulation in various dosages and that caused by the change of administration Zervixschleimes is examined (ver-same S. 429 “Abstract”, S. 430/431 cross section, S. 434 Table 2 so-such as S. 436 Abs. 1). These are factors to, both - with regard to the inhibition of ovulation - for the development of a combination preparation as well as for the development of a single preparation are substantially (vg. B12 An-position 6 S. A-55 li./re. Sp. cross section mirror points 1 and 3). The single-wall of the defendant, in the study of Zervixschleimes, with its altered permeability'll measured for sperm after progestin administration, places the situation only to an in vitro experiment, clarified the classification here-in is not appropriate for a restricted for the purpose of developing a Monoprä-parates test, can not access. For the examination of body fluids is usually based on in vitro measurements, because - this is especially the case here - in-vivo measurements for threaded-voltage reproducible values based on body fluids, which are left in their Natürli-chen environment, in general, are not practical. Also referred to in the document has been examined NiK3 period within which the change of the cerium-vixschleimes – the 13. to 14. Day of cycle – can not support the argument of the defendant. This is the cycle center, in which ovulation occurs, d. h. to such period in which the change in the consistency Zervixschleimes under progestin administration is another essential factor for the contraceptive effect of this drug group.
Although the publication NiK4 relates exclusively to studies ovulationshemmen-the effect of desogestrel (= Org 2969), but even these can be seen here in a general context. Examines Namely particular kind-
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flussung that natural hormones, that play a role in the context of the control of the menstrual cycle (vgl. S. 51 “Abstract”, S. 54 Figure 2 and Tab. I and S. 55 Figure 3), d. h. Effects, their knowledge for the development of ever-contraceptive preparation, whether it is a combination product or a monopreparation, is much. However, the predictive value of this document is provided in-even beyond those of the document NiK3, as is smitten before-there eventually, conduct additional clinical trials with desogestrel alone or in combination with an estrogen-nation (vgl. S. 57 Abs. 1). Therefore, the expert will not read solely with professional designed the studies described in this document for the development of a combination product, son-rather the closing remarks, merely means erach th as an indication, that the progestin desogestrel is seen by experts as a suitable candidate for both a combination product as well as a monopreparation.
The argument of the defendant is also true not to the publication NiK2 to. Because of this, the authors not only explicitly on a continuous low-dose progestin- or. “Progestogen-only”-Intake at the Immaculate Conception prevention reference (vgl. S. 21 to. Sp. Abs. 1 and S. 27 re. Sp. Abs. 3). The studies described in this scientific article also those egg-properties of desogestrel be investigated, that are essential for the action of a mono-nen based Gestage preparation (vgl. S. 21 "Abstract" and S. 27 to. Sp. „Ovulation inhibition by desogestrel“, re. Sp. „Effects on cervical mucus“ sowie „Effects on the endometrium“ i. In. m. B12 conditioning 6 S. A 55 to. / king. Sp. on cross-paragraph). Moreover, in this document - as indeed in the publications NiK3 and NiK4 – those side effects subject of investiga-tion, where it is irregular bleeding between periods and are characteristic in connection with the use of HRT (vgl. NiK2 S. 21 “Abstract” Abs. 3, S. 24/25 side cross-section, S. 26 re. Sp. Abs. 1 From. 3 and 4, Abs. 5 prov. Set). On the other hand is taken in this document at any point on the use of desogestrel as active component of a combina-onspräparates reference. The put forward in connection with this Do-ument argument, here also am only the inhibition of ovulation
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and thus the development of a combination product in focus, because the measurement of the change in permeability for sperm was in accordance with the progestin-only transfer in vitro, for the reasons mentioned above also lead to a different point of view we-nig, as the reference to Figures 2A to 2D and 3A to 3D. Since, according to this - put forward as the defendant – the cerium vixschleim after the desogestrel-taking in too small an amount was available and was too viscous, to those test, with the transmission of sperm can be ge-measure, conduct at all, are the data obtained in this together-hang incomplete, why the focus is clearly not aimed at the development of HRT. The reduction in the mucus in the cervix and the increase in the viscosity of the cerium vixschleimes are but - and this is attributed to the general knowledge of the skilled man - already a characteristic feature of a progestational contraceptive effect (vgl. NiK2 S. 27 re. Sp. Abs. 2).
The defendant also argued, the publications NiK2 NiK4 to be directed on delivering a combination product, because the specified there taking periods of 21 or. 23 Coincided with the day time patterns of combination products, during monotherapy components - as can be seen based on the findings B15 is - at least 28 Day should be administered. For in the case of a single specimen viewing egg-nes administration time period of three weeks leave not a guarantee of long-term stability of the cycle or a contraceptive effect to. This one-wall can not grip also. The studies described in the publications NiK2 to NiK4 is the first clinical studies of desogestrel, which is only checked, what influence the intake of desogestrel in the female cycle regulatory hormones, in particular-ticular how those factors are influenced, with which a pregnant scape can be prevented, and the extent to which intake optionally leads to undesirable side effects (vgl. B15 S. 4 Abs. 1 Set 3 in. in.). The results thus obtained are capable to those skilled then a suggestion to convey meaning-going, such a drug already under investigation for further develop--
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to take into account developments. However, they are not intended to, To provide data on cycle control while taking desogestrel, since such studies in each case - as well as for combination products - would have to be of longer duration-th (vgl. this also B10 S. 5/6 page border set and B13 S. 7 Abs. 2 Set 1). Studies on cycle control for an extended period of time and thus to a permanent Ovulationsinhibierung are apparent to those skilled but only reasonable and appropriate, if he [- Is the way it is done with the publications NiK2 to NiK4 -] based on the results from preliminary experiments – can expect the success ge-wanted and need not be expected to experience adverse side effects open-clear.
In addition, the defendant has argued, the priorities of the publications NiK2 to NiK4 on the inhibition of ovulation and thus the development of a combination product-lung was also evident, because in all the documents-sen on the studies published by scientific article B11 reference being made and will received under the described therein investigations shall desogestrel in combination with an estrogen. Meanwhile, this argument does not convince the Senate. As stated in the publication B11, shows the experimental arrangement described there is a good model for initial investigations progestational agents are (vgl. S. 18 re. Sp. Abs. 2 the. Set). For the participants of this study was to women, whose ovaries had been removed, thus women whose estrogen production is no longer that of women ent-spoke with intact ovaries. But this is at these study participants before a by-Estr genmangel related changes in mucus production in the cervix so-how of the endometrium. In order to study under these conditions, the effect of a Ge-stagens on precisely these factors, it is therefore necessary, establish appropriate conditions again taking an estrogen approximately women with normal estrogen production-tion (vgl. S. 14 re. Sp. Abs. 1 and 2). The results obtained with such a study can not be compared with the results of this reason,, obtained under the administration of a combination product of women with intact ovaries. This is
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Moreover, also does not correspond to the objective of the corresponding scale Stu, To obtain evidence on the effect of desogestrel in a combined oral contraceptive in healthy women.
Finally, the defendant has objected, providing a single preparation containing desogestrel for solving the present problem is not refer to an inventive step based, because this only in the year 1990 was applied for a patent, while the documents NiK2 to NiK4 al-ready in the years 1976, 1977 and 1982 were published. How vorste-based forth, was the provision of the disputed claim 1 angege surrounded desogestrel-containing mono-preparation having regard to the documents NiK2 to NiK4 close. Therefore, it is in this case neither a long-standing unsolved problem or a long effort to find a solution, still a long working with adverse solutions from the present state of the art to recognize (vgl. Bus / Keukenschrijver Patent Law 7. Ed. § 4 Rdn. 173).
1.4. The subject matter of claim 1 according to basic patent is not for lack of inventive step was capable.
2. A viability, the Senate also not in the objects of the independent claims 5, 6, 7 and 8 recognize. They are therefore even-if annul.
2.1. The claims 5, 6 and 7 are the use of a daily oral dosage unit, a drug delivery system comprising a package, the 26 to 30 containing sequential daily dosage units, as well as a contraception-hütungspackung the type, includes the daily dose of progestogen-only units, directional, wherein the dosage unit respectively as the only contraceptive Be an integral part desogestrel, 3-Contains ketodesogestrel or mixtures thereof. Since this is Konfektionierungen, policies currently under discussion in the therapeutic area are common, relate these claims no other
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Facts, as he with the claim 1 present, which is why the patent-claim 1 also considered reasons indicated herein incorporated.
2.2. The claim 8 relates to a process for preparing a drug delivery system, the formulation of the desogestrel, 3-Ketodeso-gestrel or mixtures thereof containing mono-preparations, and includes the Kon-fektionierung. At no point in the contested patent an indication is given as-executed starting, it has been necessary considerations innovative style, to take the measures specified there. Rather, it involves procedures, which are common to those skilled in the art, therefore, also in this context,.
2.3. Also in the articles of the respective dependent patent claims-che 2, 3 and 9 can not be seen was capable rest. The defendant has not claimed, that they would come to a stand-alone-patentable content. These claims, their independent inventive content was provided by the applicant stating the reasons to deny, are therefore also not patentable.
III.
The question, whether the supplementary protection certificate could be explained also void, because it is contrary to the provisions of Article 3 Regulation (EG) No.. 469/2009 has been granted, since the authorization for placing the product desogestrel as pharmaceuticals in Germany, due to which the Er distribution was carried out, not the first authorization for placing the He-desogestrel testimony was as pharmaceuticals in Germany, can therefore be left open.
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IV.
The cost is based on § 84 Abs. 2 PatG i. In. m. § 91 Code of Civil Procedure. The de-decision on provisional enforceability is issued on the basis of § 99 Abs. 1 PatG i. In. m. § 709 Set 1 and 2 Code of Civil Procedure.
Right to appeal
Against this judgment the appeal of appeal can not be.
The notice of appeal must be signed by a person in the Federal Republic of Germany zugelas-nected lawyer or patent attorney or a licensed professional in the Federal Republic of Germany lawyer or patent attorney and within a month the Bundesgerichtshof, Herrenstraße 45a, 76133 Charles calm submitted. The appeal period begins with the delivery of the documents drawn up in full-constant form of judgment, but no later than the expiration of five Mon-ordinates after the promulgation.
The notice of appeal must include the name of the judgment, against which the appeal is directed, and include a statement, that against this ruling will loaded.
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