Wednesday, April 8, 2009
Dutch court held all the claims of Lundbeck’s escitalopram patent and SPCs invalid
Decision available only in dutch..here -- in Dutch.
Saturday, April 4, 2009
Wyeth's application for Venlafaxine XR generics identity discovery in Australia denied
In January 2009, Wyeth filed an application in the Federal Court seeking preliminary discovery from the Department pursuant to O 15A of the Federal Court Rules of the names of the persons who have applied to the ARTG and for documentary information relating to those applications. Until early March this year, Efexor-XR was the only brand of venlafaxine registered by the Australian Register of Therapeutic Goods (“ARTG”). However, towards the end of last year, Wyeth apparently suspected that other companies had applied to the ARTG to register medicines containing venlafaxine. Wyeth therefore requested the Department of Health and Ageing (“the Department”) to provide it with information under the Freedom of Information Act 1982 (Cth) (the “FOI Act”) in relation to those applications.
Under the relevant provisions of the National Health Act 1953 (Cth), the effect of a listing of the generics on the PBS will be to apply a 12.5% price reduction to the generics and to the three varieties of Efexor-XR marketed by Wyeth. It is the prospect of this price reduction, and the administrative processes involved in implementing it, which underlies Wyeth’s desire for early resolution of the question of whether the marketing of the generics would constitute an infringement of Wyeth’s method patent. Thus, Wyeth seeks to obtain preliminary discovery at the earliest possible date, in order to provide the foundation for injunctive proceedings, including a claim for interlocutory injunctive relief.
When analyzing Wyeth’s evidence as to prospects of success, Court stated that
· Patent claims “A method of providing a therapeutic blood plasma concentration of venlafaxine over a 24 hour period ... that provides a peak blood plasma level of venlafaxine in from about 4 to 8 hours after administration”
Section 4.3.1 of the ARGPM goes on to say that applications for essentially similar medicines can be made in Australia under a number of different circumstances. These include:-in lieu of safety and efficacy data, an appropriate bioavailability study or studies should normally be submitted. Provided that the essentially similar product has a sufficiently similar plasma concentration/time profile to a leading brand in Australia, the two products may be considered bioequivalent. (emphasis added)
· There was no medical evidence to support the proposition that the pharmacology of venlafaxine hydrochloride is such that it lends itself to only one possible method of achieving the same time/peak blood concentration as is produced in Efexor-XR.
The court however denied Wyeth’s motion stating the following
“it is not in the interests of justice to order identity discovery on this application. There are two reasons for this. First, I am not satisfied on the evidence before me that Wyeth has good prospects of success at a final hearing. The most that can be said is that it has a provisional working hypothesis which would need to be supplemented by further evidence, including expert evidence, to determine the strength of Wyeth’s case.Moreover, there are a number of factors which suggest that the hypothesis is not correct, or, at least, that those factors cannot be displaced in the absence of further evidence. I referred to them at . Second, the assumption which underlies Wyeth’s claim for identity discovery is that if I were to make an order now, it would be in a position to have a claim for interlocutory relief determined by 20 July 2009. This is the date which is shown in Wyeth’s chronology of steps required for it to obtain information discovery and, thereafter, to have heard and determined a claim for interlocutory relief. The corresponding date shown on the chronology, upon the assumption that Wyeth has to wait for ARTG listing on 15 May 2009, is 2 September 2009. I cannot be confident that the Court would be in a position to give judgment on a contested claim for interlocutory relief prior to the anticipated PBS listing of the generics on 1 August 2009. It follows that in my view, the commercial inconveniences and possible difficulties in restoring Wyeth to the status quo will arise in any event.
The application for identity discovery was dismissed with costs
Under the relevant provisions of the National Health Act 1953 (Cth), the effect of a listing of the generics on the PBS will be to apply a 12.5% price reduction to the generics and to the three varieties of Efexor-XR marketed by Wyeth. It is the prospect of this price reduction, and the administrative processes involved in implementing it, which underlies Wyeth’s desire for early resolution of the question of whether the marketing of the generics would constitute an infringement of Wyeth’s method patent. Thus, Wyeth seeks to obtain preliminary discovery at the earliest possible date, in order to provide the foundation for injunctive proceedings, including a claim for interlocutory injunctive relief.
When analyzing Wyeth’s evidence as to prospects of success, Court stated that
· Patent claims “A method of providing a therapeutic blood plasma concentration of venlafaxine over a 24 hour period ... that provides a peak blood plasma level of venlafaxine in from about 4 to 8 hours after administration”
Section 4.3.1 of the ARGPM goes on to say that applications for essentially similar medicines can be made in Australia under a number of different circumstances. These include:-in lieu of safety and efficacy data, an appropriate bioavailability study or studies should normally be submitted. Provided that the essentially similar product has a sufficiently similar plasma concentration/time profile to a leading brand in Australia, the two products may be considered bioequivalent. (emphasis added)
· There was no medical evidence to support the proposition that the pharmacology of venlafaxine hydrochloride is such that it lends itself to only one possible method of achieving the same time/peak blood concentration as is produced in Efexor-XR.
The court however denied Wyeth’s motion stating the following
“it is not in the interests of justice to order identity discovery on this application. There are two reasons for this. First, I am not satisfied on the evidence before me that Wyeth has good prospects of success at a final hearing. The most that can be said is that it has a provisional working hypothesis which would need to be supplemented by further evidence, including expert evidence, to determine the strength of Wyeth’s case.Moreover, there are a number of factors which suggest that the hypothesis is not correct, or, at least, that those factors cannot be displaced in the absence of further evidence. I referred to them at . Second, the assumption which underlies Wyeth’s claim for identity discovery is that if I were to make an order now, it would be in a position to have a claim for interlocutory relief determined by 20 July 2009. This is the date which is shown in Wyeth’s chronology of steps required for it to obtain information discovery and, thereafter, to have heard and determined a claim for interlocutory relief. The corresponding date shown on the chronology, upon the assumption that Wyeth has to wait for ARTG listing on 15 May 2009, is 2 September 2009. I cannot be confident that the Court would be in a position to give judgment on a contested claim for interlocutory relief prior to the anticipated PBS listing of the generics on 1 August 2009. It follows that in my view, the commercial inconveniences and possible difficulties in restoring Wyeth to the status quo will arise in any event.
The application for identity discovery was dismissed with costs
Ranbaxy prevents crystalline adefovir dipivoxil patent grant in India
Gilead’s 712/del/2002 application relates to a crystalline adefovir dipivoxil. AD is the bis pivaloyloxmethyl ester of the parent compound 9-[2-[[bis[(pivaloyloxy)-methoxy]phosphinyl]methoxy]ethyl]adenine,(PMEA) and the method of preparation thereof. The compound is active against Hepatitis B virus. Both the parent compound and the ester are well known in art.
The claim 1 at issue was directed to crystalline AD which may be selected from anhydrous with specific monoclinic cell parameters and XRD, hydrate with specific XRD and DSC, methanol solvate with specific XRD and DSC, fumaric acid salt with specific XRD and DSC.
Opponent Ranbaxy ‘s basis for opposition was majorly based on section 3(d) - polymorph of AD, it will be regarded as the same substance unless it shows enhanced efficacy over the known substance i.e. amorphous AD. Ranbaxy put forth that the applicant had submitted that the crystalline AD form has – good melting point and/or bulk density properties facilities manufacturing and formulation of compositions containing AD: at least 97%(w/w) purity and enhanced dissolution rate and submitted that since all these relate to physical properties of the compound, therapeutic efficacy is not established. Controller stated “I have analyzed the results as provided by the applicants regarding improved stability of the alleged compound. I have observed that the applicants have not provided a comparative data with respect to the amorphous/parent compound of the alleged invention. Also no improvement in the therapeutic efficacy of AD as compared to its parent compound (PMEA) has been provided. In fact both the compounds (AD) is used to treat viral infections which is also the activity shown by the parent compound (PMEA). In view of above I state that the subject matter for application no. 712/DEL/2002 is not patentable under section 3(d)”
With respect to Novelty all the prior arts relied upon were silent on crystalline AD. Hence the controller stated “Since, the Opponent failed to present or identify any document in this context, the ground of lack of novelty under Section 25(1)(b) taken by the Opponent is not maintainable and hence should be rejected. I would thus hold the compound to be novel”
With respect to the invention step controller stated “I find that various cited documents especially US4808716 and US5663159 synthesise the parent compound (PMEA) as a crystalline solid. Since the compound of the invention (AD) is an ester form of the parent compound (PMEA) no inventive technical advancement can be attributed to the alleged invention. I have analysed the results as provided by the applicants regarding improved stability of the alleged compound. I have observed that the applicants have not provided a comparative data with respect to the amorphous/parent compound of the alleged invention. In the absence of the same an inventive step cannot be established."
The claim 1 at issue was directed to crystalline AD which may be selected from anhydrous with specific monoclinic cell parameters and XRD, hydrate with specific XRD and DSC, methanol solvate with specific XRD and DSC, fumaric acid salt with specific XRD and DSC.
Opponent Ranbaxy ‘s basis for opposition was majorly based on section 3(d) - polymorph of AD, it will be regarded as the same substance unless it shows enhanced efficacy over the known substance i.e. amorphous AD. Ranbaxy put forth that the applicant had submitted that the crystalline AD form has – good melting point and/or bulk density properties facilities manufacturing and formulation of compositions containing AD: at least 97%(w/w) purity and enhanced dissolution rate and submitted that since all these relate to physical properties of the compound, therapeutic efficacy is not established. Controller stated “I have analyzed the results as provided by the applicants regarding improved stability of the alleged compound. I have observed that the applicants have not provided a comparative data with respect to the amorphous/parent compound of the alleged invention. Also no improvement in the therapeutic efficacy of AD as compared to its parent compound (PMEA) has been provided. In fact both the compounds (AD) is used to treat viral infections which is also the activity shown by the parent compound (PMEA). In view of above I state that the subject matter for application no. 712/DEL/2002 is not patentable under section 3(d)”
With respect to Novelty all the prior arts relied upon were silent on crystalline AD. Hence the controller stated “Since, the Opponent failed to present or identify any document in this context, the ground of lack of novelty under Section 25(1)(b) taken by the Opponent is not maintainable and hence should be rejected. I would thus hold the compound to be novel”
With respect to the invention step controller stated “I find that various cited documents especially US4808716 and US5663159 synthesise the parent compound (PMEA) as a crystalline solid. Since the compound of the invention (AD) is an ester form of the parent compound (PMEA) no inventive technical advancement can be attributed to the alleged invention. I have analysed the results as provided by the applicants regarding improved stability of the alleged compound. I have observed that the applicants have not provided a comparative data with respect to the amorphous/parent compound of the alleged invention. In the absence of the same an inventive step cannot be established."
Glatiramer acetate( copolymer-1) application fails to qualify the section 3(d) of the Indian Patent Act
Application at issue- “A co-polymer fraction-1”, application number 93/DEL/2003, assigned to Yeda Research/ Teva.
Opponent Natco submitted that the copolymer-1 with the exact amino acid composition & mole ratio (alanine/glutamic acid/lysine /tyrosine as 6:2:5:1) as claimed in the present invention is already described and published in 1971 vide European Journal. Immunol, 1971,1;242-248.The same product has been patented as US 3849550 (Nov 19,1974) with the title “Therapeutic copolymer “ having the same composition mentioned above.
The only contribution in the current invention apparently is the manipulation of the molecular weight of the copolymer-1. In 93/DEL/2003 application applicants had demonstrated that low molw weight polymer (7.3 & 8.4 kDa) were less toxic as compared to prior art high molecular weight (22kDa) polymers.
Natco cited a reference clinical trial data reported in “New England Journal of Medicine” of 1987 which reported that copolymer-1 with molecular weight between 14 kDa to 23kDa was found to be non-toxic during short term and long term administration in mice, rabbit and dogs. Teva in their reply stated that the New England Journal of Medicine 1987, did not provide any satisfactory or sound argument with respect to the serious discrepancy pointed out and that they only tried to conclude that the data referring to 60% death of mice showed that the material would have toxicity in humans although it may not cause death. Controller however was not persuaded with this argument of Teva’s.
Natco also relied upon a second document EP-383620 which discloses that the product of molecular weight in the range of 5-50 kDa synthesized by polymerizing alanine, glutamic acid, lysine and tyrosine or tryptophan . This prior art teaches that copolymer-1 comprises random amino acid sequences mixture, which is non-uniform with respect to amino acid and having average molecular weight 23 kDa. Natco argued that combining the teaching of these two citations a person skilled in the art would obviously be motivated to further reduce the molecular weight of the copolymer-1 to reduce further toxicity. The prior art mentioned that the best results have been found for copolymer of 23 kDa or lower range preferably 14 to 23 kDa. Therefore it would be obvious for a person skilled in the art to further decrease the molecular weight copolymer-1, than known in the art with reduced toxicity.
Controller stated the following
“Copolymer-1 of the prior art as well as of the present invention is a potential therapeutic agent for multiple sclerosis & known for long. The applicant in the present invention has modified/ isolated the prior art copolymer-1 by known method like chromatography, acid/enzymatic hydrolysis etc. to obtain a lower average molecular weight copolymer-1 species particularly in the range of 2-20 kDa with no more than 5% species having molecular weight above 40 kDa.
The selection of lower average molecular weight copolymer-1 was motivated from three prior arts cited by Natco” emphasis added
Controller also stated that Applicant’s experimental report is not reliable, further experimental evidence should have been forwarded at least during prosecution, particularly on the face of it being contradictory to the report of annexure 7 as well as the inferences shown in Annexure 3 and prior art EP/0383620 specification of copolymer-1.
Finally it was concluded that the present invention is definitely a selection from the prior art, & is a subject of section 3(d) being a product, made up of component species. Every selection will lack in inventiveness if it is not accompanied by surprising efficacious effect. The specification of the present invention does not provide any such effect. The toxicity analysis appears to be inadequate and applicant ought to have forwarded more evidences of its experiments. Therefore under section 3(d) of the Indian Patent Act which takes cognizance of such modification under this section , is not satisfied or in other word the requirement of this section not fulfilled. The application fails to qualify the section 3(d) of the Indian Patent Act and is obvious and does not contain an inventive step.
Opponent Natco submitted that the copolymer-1 with the exact amino acid composition & mole ratio (alanine/glutamic acid/lysine /tyrosine as 6:2:5:1) as claimed in the present invention is already described and published in 1971 vide European Journal. Immunol, 1971,1;242-248.The same product has been patented as US 3849550 (Nov 19,1974) with the title “Therapeutic copolymer “ having the same composition mentioned above.
The only contribution in the current invention apparently is the manipulation of the molecular weight of the copolymer-1. In 93/DEL/2003 application applicants had demonstrated that low molw weight polymer (7.3 & 8.4 kDa) were less toxic as compared to prior art high molecular weight (22kDa) polymers.
Natco cited a reference clinical trial data reported in “New England Journal of Medicine” of 1987 which reported that copolymer-1 with molecular weight between 14 kDa to 23kDa was found to be non-toxic during short term and long term administration in mice, rabbit and dogs. Teva in their reply stated that the New England Journal of Medicine 1987, did not provide any satisfactory or sound argument with respect to the serious discrepancy pointed out and that they only tried to conclude that the data referring to 60% death of mice showed that the material would have toxicity in humans although it may not cause death. Controller however was not persuaded with this argument of Teva’s.
Natco also relied upon a second document EP-383620 which discloses that the product of molecular weight in the range of 5-50 kDa synthesized by polymerizing alanine, glutamic acid, lysine and tyrosine or tryptophan . This prior art teaches that copolymer-1 comprises random amino acid sequences mixture, which is non-uniform with respect to amino acid and having average molecular weight 23 kDa. Natco argued that combining the teaching of these two citations a person skilled in the art would obviously be motivated to further reduce the molecular weight of the copolymer-1 to reduce further toxicity. The prior art mentioned that the best results have been found for copolymer of 23 kDa or lower range preferably 14 to 23 kDa. Therefore it would be obvious for a person skilled in the art to further decrease the molecular weight copolymer-1, than known in the art with reduced toxicity.
Controller stated the following
“Copolymer-1 of the prior art as well as of the present invention is a potential therapeutic agent for multiple sclerosis & known for long. The applicant in the present invention has modified/ isolated the prior art copolymer-1 by known method like chromatography, acid/enzymatic hydrolysis etc. to obtain a lower average molecular weight copolymer-1 species particularly in the range of 2-20 kDa with no more than 5% species having molecular weight above 40 kDa.
The selection of lower average molecular weight copolymer-1 was motivated from three prior arts cited by Natco” emphasis added
Controller also stated that Applicant’s experimental report is not reliable, further experimental evidence should have been forwarded at least during prosecution, particularly on the face of it being contradictory to the report of annexure 7 as well as the inferences shown in Annexure 3 and prior art EP/0383620 specification of copolymer-1.
Finally it was concluded that the present invention is definitely a selection from the prior art, & is a subject of section 3(d) being a product, made up of component species. Every selection will lack in inventiveness if it is not accompanied by surprising efficacious effect. The specification of the present invention does not provide any such effect. The toxicity analysis appears to be inadequate and applicant ought to have forwarded more evidences of its experiments. Therefore under section 3(d) of the Indian Patent Act which takes cognizance of such modification under this section , is not satisfied or in other word the requirement of this section not fulfilled. The application fails to qualify the section 3(d) of the Indian Patent Act and is obvious and does not contain an inventive step.
Friday, April 3, 2009
Napp N Sandoz, Ratiopharma- Oxycodone patents Valid in UK
Broadly, the two patents in suit are for a 12-hour controlled release form of oxycodone. The claims alleged to be infringed by the Cimex product are for barrier-type controlled release forms. The barrier-type form specifically described is made by the use of extrusion spheronisation, one of a number of well-known way of making small spherical particles. The description also includes matrix-type forms .
Generic’s tablets of oxycodone contained small particles made up of a number of layers (supplied to the generic companies by Cimex). The core of these particles is made from sugar crystals. There is then an inner layer of made up of oxycodone hydrochloride (83% wt), hydroxypropylmethyl cellulose (HPMC, about 8% wt) and talc/macrogol (about 9% wt). A further polymer layer contains ethyl cellulose, hydroxypropylcellulose and propylene glycol. The polymer layer controls the release of the oxycodone hydrochloride in the inner layer. A further outermost layer contains about 96% wt oxycodone hydrochloride and about 4% wt HPMC. About 20% of the total weight of oxycodone hydrochloride is in the outermost layer.
In the generics’s product 20% of the oxycodone is on the outside of the particles and 80% is within. The 20% will be released more or less immediately whereas the 80% will be slow-released through the polymer layer. By contrast the key difference from what is specifically described in the patents is that in the latter all the oxycodone is inside a polymer layer and will be control-released.
Infringement:
Ratiopharm and Sandoz- did not admit that the Cimex tablets comprised "spheroids" or a "spheronising agent". They pleaded that the term "spheroids" denoted spherical granules manufactured by spheronisation and that none of the excipients constituted a "spheronising agent". The inner and outer layers contain HPMC, about 8 wt% and 4 wt% respectively. They say that the water-soluble HPMC serves as a binder and is not a spheronising agent
Court- interpreted "spheroid" was not limited to the process by which the product was made and also stated that water soluble polymer such as HPMC was suitable for four out of the five spheronisation processes known at the priority date for producing spheroids for a controlled release formulation: (1) fluidised-bed granulation; (2) rotor granulation; (3) extended wet granulation; and (4) non-pareil beads (the Cimex process).Hence the generic process infringed the claims.
Ratiopharm and Sandoz- argued that the claims do not extend to a form of dosage in which some of the oxycodone is on the outside of the coating. This question arises because the Cimex product has an external layer on its spheroids consisting of about 20% of the drug, which is released immediately, the remaining 80% being within the coating which controls its release.
Court - concluded that there is nothing in the claim language that excludes a tablet which has all the characteristics it sets out, but with the additional feature of an external application of oxycodone. There is also nothing in the teaching in the patent to suggest that such a tablet was intended to be excluded. Nor is there any commercial or technical reason for thinking that the patentee would have wanted to exclude an otherwise infringing article with such an additional feature.
Further with respect to claimed dissolution profiles, the issue between the parties was - does the claim call for the whole of the test procedure in the USP, including the acceptance test, to be carried out so that the claim only covers that which passes the acceptance test, or is it sufficient if an individual dosage form passes the test? The point matters because only a modest (7%, nonetheless significant) proportion of the Cimex tablets have dissolution rates within integer 1(d). If the true construction of this feature requires compliance with the USP acceptance requirements there is no infringement, even though a proportion of the tablets, as individual tablets, do comply with the rates set out in the claim.
Court concluded that the claim is for a dosage form. It is a dosage form which must past the test. On the r/S construction one would have to test at least 6 tablets and possibly up to 24 tablets. And one could then decide whether the batch of tablets from which these were taken satisfy the criteria. Hence the generic falls within the scope of the claims.
Invalidity:
Sandoz and ratiopharm said the patents were invalid in respect of added matter under Article 123 of the European Patent Convention ("(2) A European patent application or a European patent may not be amended in such a way that it contains subject-matter which extends beyond the content of the application as filed") and under the Patents Act 1977 ("Since our provisions mean the same as Art 123(2) there is no point in referring to them"). The argument of invalidity was that parts of the specification and/or claims of 730 had not been disclosed clearly and unambiguously in Napp's PCT application and/or that they did not provide a technical contribution.
However court concluded "A feature which has not been disclosed in the application as filed but which has been added to the application during examination and which, without providing a technical contribution to the subject-matter of the claimed invention, merely limits the protection conferred by the patent as granted by excluding protection for part of the subject-matter of the claimed invention as covered by the application as filed, is not to be considered as subject-matter which extends beyond the content of the application as filed within the meaning of Article 123(2) EPC. The ground for opposition under Article 100(c) EPC therefore does not prejudice the maintenance of a European patent which includes such a feature"
UK appeal court also addressed the opposite verdict reached by german courts earlier and stated that “We are not persuaded by either of these decisions, even though we give great respect to the decisions of the German courts”
Generic’s tablets of oxycodone contained small particles made up of a number of layers (supplied to the generic companies by Cimex). The core of these particles is made from sugar crystals. There is then an inner layer of made up of oxycodone hydrochloride (83% wt), hydroxypropylmethyl cellulose (HPMC, about 8% wt) and talc/macrogol (about 9% wt). A further polymer layer contains ethyl cellulose, hydroxypropylcellulose and propylene glycol. The polymer layer controls the release of the oxycodone hydrochloride in the inner layer. A further outermost layer contains about 96% wt oxycodone hydrochloride and about 4% wt HPMC. About 20% of the total weight of oxycodone hydrochloride is in the outermost layer.
In the generics’s product 20% of the oxycodone is on the outside of the particles and 80% is within. The 20% will be released more or less immediately whereas the 80% will be slow-released through the polymer layer. By contrast the key difference from what is specifically described in the patents is that in the latter all the oxycodone is inside a polymer layer and will be control-released.
Infringement:
Ratiopharm and Sandoz- did not admit that the Cimex tablets comprised "spheroids" or a "spheronising agent". They pleaded that the term "spheroids" denoted spherical granules manufactured by spheronisation and that none of the excipients constituted a "spheronising agent". The inner and outer layers contain HPMC, about 8 wt% and 4 wt% respectively. They say that the water-soluble HPMC serves as a binder and is not a spheronising agent
Court- interpreted "spheroid" was not limited to the process by which the product was made and also stated that water soluble polymer such as HPMC was suitable for four out of the five spheronisation processes known at the priority date for producing spheroids for a controlled release formulation: (1) fluidised-bed granulation; (2) rotor granulation; (3) extended wet granulation; and (4) non-pareil beads (the Cimex process).Hence the generic process infringed the claims.
Ratiopharm and Sandoz- argued that the claims do not extend to a form of dosage in which some of the oxycodone is on the outside of the coating. This question arises because the Cimex product has an external layer on its spheroids consisting of about 20% of the drug, which is released immediately, the remaining 80% being within the coating which controls its release.
Court - concluded that there is nothing in the claim language that excludes a tablet which has all the characteristics it sets out, but with the additional feature of an external application of oxycodone. There is also nothing in the teaching in the patent to suggest that such a tablet was intended to be excluded. Nor is there any commercial or technical reason for thinking that the patentee would have wanted to exclude an otherwise infringing article with such an additional feature.
Further with respect to claimed dissolution profiles, the issue between the parties was - does the claim call for the whole of the test procedure in the USP, including the acceptance test, to be carried out so that the claim only covers that which passes the acceptance test, or is it sufficient if an individual dosage form passes the test? The point matters because only a modest (7%, nonetheless significant) proportion of the Cimex tablets have dissolution rates within integer 1(d). If the true construction of this feature requires compliance with the USP acceptance requirements there is no infringement, even though a proportion of the tablets, as individual tablets, do comply with the rates set out in the claim.
Court concluded that the claim is for a dosage form. It is a dosage form which must past the test. On the r/S construction one would have to test at least 6 tablets and possibly up to 24 tablets. And one could then decide whether the batch of tablets from which these were taken satisfy the criteria. Hence the generic falls within the scope of the claims.
Invalidity:
Sandoz and ratiopharm said the patents were invalid in respect of added matter under Article 123 of the European Patent Convention ("(2) A European patent application or a European patent may not be amended in such a way that it contains subject-matter which extends beyond the content of the application as filed") and under the Patents Act 1977 ("Since our provisions mean the same as Art 123(2) there is no point in referring to them"). The argument of invalidity was that parts of the specification and/or claims of 730 had not been disclosed clearly and unambiguously in Napp's PCT application and/or that they did not provide a technical contribution.
However court concluded "A feature which has not been disclosed in the application as filed but which has been added to the application during examination and which, without providing a technical contribution to the subject-matter of the claimed invention, merely limits the protection conferred by the patent as granted by excluding protection for part of the subject-matter of the claimed invention as covered by the application as filed, is not to be considered as subject-matter which extends beyond the content of the application as filed within the meaning of Article 123(2) EPC. The ground for opposition under Article 100(c) EPC therefore does not prejudice the maintenance of a European patent which includes such a feature"
UK appeal court also addressed the opposite verdict reached by german courts earlier and stated that “We are not persuaded by either of these decisions, even though we give great respect to the decisions of the German courts”
Application of KSR in Biotechnology- IN RE MAREK Z. KUBIN and RAYMOND G. GOODWIN( April 03 , 2009)
This case presents a claim to a classic biotechnology invention – the isolation and sequencing of a human gene that encodes a particular domain of a protein. Specifically, appellants claim DNA molecules (“polynucleotides”) encoding a protein (“polypeptide”) known as the Natural Killer Cell Activation Inducing Ligand (“NAIL”).
Natural Killer (“NK”) cells, thought to originate in the bone marrow, are a class of cytotoxic lymphocytes that play a major role in fighting tumors and viruses. NK cells express a number of surface molecules which, when stimulated, can activate cytotoxic mechanisms. NAIL is a specific receptor protein on the cell surface that plays a role in activating the NK cells.
The specification of the claimed invention recites an amino acid sequence of a NAIL polypeptide. The invention further isolates and sequences a polynucleotide that encodes a NAIL polypeptide. Moreover, the inventors trumpet their alleged discovery of a binding relationship between NAIL and a protein known as CD48. The NAIL-CD48 interaction has important biological consequences for NK cells, including an increase in cell cytotoxicity and in production of interferon.
Appellants claim a genus of isolated polynucleotides encoding a protein that binds CD48 and is at least 80% identical to amino acids 22-221 of SEQ ID NO:2 – the disclosed amino acid sequence for the CD48-binding region of NAIL. Apart from disclosing two polynucleotides falling within the scope of the claimed genus, specification also contemplates variants of NAIL that retain the same binding properties( however the specification does not indicate any example variants of NAIL that make conservative amino acid substitutions). Based on this the board raised a 112 rejection.
Under 103, the Board rejected appellants’ claims over the combined teachings of U.S. Patent No. 5,688,690 (“Valiante”) , 2 Joseph Sambrook et al., Molecular Cloning: A Laboratory Manual 43-84 (2d ed. 1989) (“Sambrook”) & Mathew et al., Cloning and Characterization of the 2B4 Gene Encoding a Molecule Associated with Non-MHC-Restricted Killing Mediated by Activated Natural Killer Cells and T Cells, 151 J. Immunology 5328-37 (1993) (“Mathew”).. Valiante discloses a receptor protein called “p38” that is found on the surface of human NK cells. Valiante also discloses and claims a monoclonal antibody specific for p38 called “mAB C1.7.” The Board found (and appellants do not dispute) that Valiante’s p38 protein is the same protein as NAIL. Sambrook, incorporated by reference in Valiante, describes methods for molecular cloning. Sambrook does not discuss how to clone any particular gene, but provides detailed instructions on cloning materials and techniques. The Board found that Mathew’s signaling molecule 2B4 is the murine (mouse) version of Valiante’s p38 and hence is cumulative to the teaching in Valiante and Sambrook.
Because of NAIL’s important role in the human immune response, the Board further found that “one of ordinary skill in the art would have recognized the value of isolating NAIL cDNA, and would have been motivated to apply conventional methodologies, such as those disclosed in Sambrook and utilized in Valiante, to do so.
Invoking the Supreme Court’s decision in KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Board concluded that appellants’ claim was “‘the product not of innovation but of ordinary skill and common sense,’ leading us to conclude NAIL cDNA is not patentable as it would have been obvious to isolate it.” Board Decision at 9 (citing KSR, 550 U.S. at 421).
Court stated that the record shows that the prior art teaches a protein of interest, a motivation to isolate the gene coding for that protein, and illustrative instructions to use a monoclonal antibody specific to the protein for cloning this gene. Therefore, the claimed invention is "the product not of innovation but of ordinary skill and common sense." Or stated in the familiar terms of this court’s longstanding case law, the record shows that a skilled artisan would have had a resoundingly "reasonable expectation of success" in deriving the claimed invention in light of the teachings of the prior art.
The present patent at issue may represents some minor advance in the art. But "[g]ranting patent protection to advances that would occur in the ordinary course without real innovation retards progress.” KSR, 550 U.S. at 419. “Were it otherwise patents might stifle, rather than promote, the progress of useful arts." Id. at 427. In light of the concrete, specific teachings of Sambrook and Valiante, artisans in this field, as found by the Board in its expertise, had every motivation to seek and every reasonable expectation of success in achieving the sequence of the claimed invention. In that sense, the claimed invention was reasonably expected in light of the prior art and "obvious to try."
Natural Killer (“NK”) cells, thought to originate in the bone marrow, are a class of cytotoxic lymphocytes that play a major role in fighting tumors and viruses. NK cells express a number of surface molecules which, when stimulated, can activate cytotoxic mechanisms. NAIL is a specific receptor protein on the cell surface that plays a role in activating the NK cells.
The specification of the claimed invention recites an amino acid sequence of a NAIL polypeptide. The invention further isolates and sequences a polynucleotide that encodes a NAIL polypeptide. Moreover, the inventors trumpet their alleged discovery of a binding relationship between NAIL and a protein known as CD48. The NAIL-CD48 interaction has important biological consequences for NK cells, including an increase in cell cytotoxicity and in production of interferon.
Appellants claim a genus of isolated polynucleotides encoding a protein that binds CD48 and is at least 80% identical to amino acids 22-221 of SEQ ID NO:2 – the disclosed amino acid sequence for the CD48-binding region of NAIL. Apart from disclosing two polynucleotides falling within the scope of the claimed genus, specification also contemplates variants of NAIL that retain the same binding properties( however the specification does not indicate any example variants of NAIL that make conservative amino acid substitutions). Based on this the board raised a 112 rejection.
Under 103, the Board rejected appellants’ claims over the combined teachings of U.S. Patent No. 5,688,690 (“Valiante”) , 2 Joseph Sambrook et al., Molecular Cloning: A Laboratory Manual 43-84 (2d ed. 1989) (“Sambrook”) & Mathew et al., Cloning and Characterization of the 2B4 Gene Encoding a Molecule Associated with Non-MHC-Restricted Killing Mediated by Activated Natural Killer Cells and T Cells, 151 J. Immunology 5328-37 (1993) (“Mathew”).. Valiante discloses a receptor protein called “p38” that is found on the surface of human NK cells. Valiante also discloses and claims a monoclonal antibody specific for p38 called “mAB C1.7.” The Board found (and appellants do not dispute) that Valiante’s p38 protein is the same protein as NAIL. Sambrook, incorporated by reference in Valiante, describes methods for molecular cloning. Sambrook does not discuss how to clone any particular gene, but provides detailed instructions on cloning materials and techniques. The Board found that Mathew’s signaling molecule 2B4 is the murine (mouse) version of Valiante’s p38 and hence is cumulative to the teaching in Valiante and Sambrook.
Because of NAIL’s important role in the human immune response, the Board further found that “one of ordinary skill in the art would have recognized the value of isolating NAIL cDNA, and would have been motivated to apply conventional methodologies, such as those disclosed in Sambrook and utilized in Valiante, to do so.
Invoking the Supreme Court’s decision in KSR International Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Board concluded that appellants’ claim was “‘the product not of innovation but of ordinary skill and common sense,’ leading us to conclude NAIL cDNA is not patentable as it would have been obvious to isolate it.” Board Decision at 9 (citing KSR, 550 U.S. at 421).
Court stated that the record shows that the prior art teaches a protein of interest, a motivation to isolate the gene coding for that protein, and illustrative instructions to use a monoclonal antibody specific to the protein for cloning this gene. Therefore, the claimed invention is "the product not of innovation but of ordinary skill and common sense." Or stated in the familiar terms of this court’s longstanding case law, the record shows that a skilled artisan would have had a resoundingly "reasonable expectation of success" in deriving the claimed invention in light of the teachings of the prior art.
The present patent at issue may represents some minor advance in the art. But "[g]ranting patent protection to advances that would occur in the ordinary course without real innovation retards progress.” KSR, 550 U.S. at 419. “Were it otherwise patents might stifle, rather than promote, the progress of useful arts." Id. at 427. In light of the concrete, specific teachings of Sambrook and Valiante, artisans in this field, as found by the Board in its expertise, had every motivation to seek and every reasonable expectation of success in achieving the sequence of the claimed invention. In that sense, the claimed invention was reasonably expected in light of the prior art and "obvious to try."
Ariad's NF-κB patent claims invalid for lack of written description
In the mid-1980s, the inventors of the ’516 patent discovered an important transcription factor that they named NF-κB. NF-κB is found in almost all animal cell types and is involved in cellular responses to stimuli such as stress, cytokines, free radicals, ultraviolet irradiation, oxidized LDL, and bacterial or viral antigens. NF-κB plays a key role in regulating the immune response to infection. Consistent with this role, incorrect regulation of NF-κB has been linked to cancer, inflammatory and autoimmune diseases, septic shock, viral infection, and improper immune development. NF-κB has also been implicated in processes of synaptic plasticity and memory.
The inventors of the ’516 patent realized that if NF-κB activity could be reduced artificially, it could ameliorate the harmful symptoms of diseases that trigger NF-κB activation.
Ariad claims methods comprising the single step of reducing NF-κB activity
On April 28, 2006, district court rendered a special verdict finding infringement of claims 80 and 95 with respect to Evista( raloxifene) and claims 144 and 145 with respect to Xigris. The jury also found that the asserted claims were not invalid for anticipation, lack of enablement, or lack of written description.Lilly appealed.
Lilly argues that the asserted claims are not supported by written description because the specification of the ’516 patent fails to adequately disclose how the claimed reduction of NF-κB activity is achieved.
‘516 specification hypothesizes three classes of molecules potentially capable of reducing NF-κB activity: specific inhibitors, dominantly interfering molecules, and decoy molecules. Lilly contends that this disclosure amounts to little more than a research plan, and does not satisfy the patentee’s quid pro quo.
According to Ariad, because there is no term in the asserted claims that corresponds to the molecules, it is entitled to claim the methods without describing the molecules.
CAFC found that Ariad’s legal assertion is flawed. CAFC stated that the specification must demonstrate that Ariad possessed the claimed methods by sufficiently disclosing molecules capable of reducing NF-κB activity so as to “satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed.
Specific inhibitors are molecules that are “able to block (reduce or eliminate) NF-κB binding” to DNA in the nucleus(only example of a specific inhibitor given in the specification is I-κB, it contains a vague functional description and an invitation for further research which CAFC does not consider as a written disclosure of a specific inhibitor) . Dominantly interfering molecules are “a truncated form of the NF-κB molecule.”( specification provides no example molecules of this class). Decoy molecules are “designed to mimic a region of the gene whose expression would normally be induced by NF-κB(The full extent of the specification’s disclosure of a method that reduces NF-κB activity using decoy molecules is that NF-κB “would bind the decoy” and thereby, “negative regulation can be effected”). CAFC stated that prophetic examples are routinely used in the chemical arts, and they certainly can be sufficient to satisfy the written description requirement. But this disclosure on decoy molecules is not so much an “example” as it is a mere mention of a desired outcome.
CAFC hence held asserted claims invalid for lack of written description and affirmed the district court’s ruling that the ’516 patent is not unenforceable due to inequitable conduct
The inventors of the ’516 patent realized that if NF-κB activity could be reduced artificially, it could ameliorate the harmful symptoms of diseases that trigger NF-κB activation.
Ariad claims methods comprising the single step of reducing NF-κB activity
On April 28, 2006, district court rendered a special verdict finding infringement of claims 80 and 95 with respect to Evista( raloxifene) and claims 144 and 145 with respect to Xigris. The jury also found that the asserted claims were not invalid for anticipation, lack of enablement, or lack of written description.Lilly appealed.
Lilly argues that the asserted claims are not supported by written description because the specification of the ’516 patent fails to adequately disclose how the claimed reduction of NF-κB activity is achieved.
‘516 specification hypothesizes three classes of molecules potentially capable of reducing NF-κB activity: specific inhibitors, dominantly interfering molecules, and decoy molecules. Lilly contends that this disclosure amounts to little more than a research plan, and does not satisfy the patentee’s quid pro quo.
According to Ariad, because there is no term in the asserted claims that corresponds to the molecules, it is entitled to claim the methods without describing the molecules.
CAFC found that Ariad’s legal assertion is flawed. CAFC stated that the specification must demonstrate that Ariad possessed the claimed methods by sufficiently disclosing molecules capable of reducing NF-κB activity so as to “satisfy the inventor’s obligation to disclose the technologic knowledge upon which the patent is based, and to demonstrate that the patentee was in possession of the invention that is claimed.
Specific inhibitors are molecules that are “able to block (reduce or eliminate) NF-κB binding” to DNA in the nucleus(only example of a specific inhibitor given in the specification is I-κB, it contains a vague functional description and an invitation for further research which CAFC does not consider as a written disclosure of a specific inhibitor) . Dominantly interfering molecules are “a truncated form of the NF-κB molecule.”( specification provides no example molecules of this class). Decoy molecules are “designed to mimic a region of the gene whose expression would normally be induced by NF-κB(The full extent of the specification’s disclosure of a method that reduces NF-κB activity using decoy molecules is that NF-κB “would bind the decoy” and thereby, “negative regulation can be effected”). CAFC stated that prophetic examples are routinely used in the chemical arts, and they certainly can be sufficient to satisfy the written description requirement. But this disclosure on decoy molecules is not so much an “example” as it is a mere mention of a desired outcome.
CAFC hence held asserted claims invalid for lack of written description and affirmed the district court’s ruling that the ’516 patent is not unenforceable due to inequitable conduct
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