New Patent Commissioner overturns Patent Term Extension decision by Predecessor

June 28, 2018

Manufacturers_Association_of_Israel.pngThe Manufacturers Association of Israel opposed an ex-partes decision to allow a patent term extension for Dexlansoprazole, and New Commissioner Ofer Alon has disallowed the extension accepted by his predecessor.

Background

Dexlansoprazole.pngDexlansoprazole is used for treating gastro-reflux and for treating or preventing digestive ulcers.

IL 145996 to Takeda is a patent for Dexlansoprazole that claims various crystalline forms of the salt, a pharmaceutical preparation including the forms, and methods of treatment or prevention of digestive ulcers.

After Takeda successfully obtained regulatory approval for Dexilant™. (Dexlansoprazole) which is the R enantiomer of Lansoprazole, they applied for a patent term extension, which was refused by the Deputy Chief Examiner on 30 June 2016 on the grounds that the registration of Dexlansoprazole is not the first approved medical usage of the active ingredient in Israel, as the racemic mixture of the same active ingredient (Lansoprazole) is already registered.

Left and right antiomers in a lattice arrangement.jpg

Racemic Lattice for Shoes

In a response filed on 28 August 2016, the Applicant acknowledged that the racemic mixture Lansoprazole includes the R-enantiomer Dexlansoprazole, but the R-enantiomer cannot be separated from the racemic mixture since the crystals themselves contain both the right and the left enantiomers within the same lattice, creating a new complex that is different from the separate enantiomers.

The Applicant submitted that previously registered Lansoprazole is thus not a racemic mixture but rather a racemic compound and consequently the Dexlansoprazole crystals are substantially different from those of Lansoprazole and should, therefore, be registerable.

The Applicant distinguishes between racemic mixtures and racemic compounds with reference to Mitchell AG, Racemic drugs: Racemic Mixture, Racemic Compound, or Pseudoracemate? J. Pharm Pharmaceut Sci 1(1):8-12, 1998).

Dexasportshoe Lattice Arrangement

Dexasportshoe Crystalline Structure

On 27 October 2016, the Deputy Chief Examiner understood the argument as stressing that the enantiomer is more efficacious than the racemic mixture and rejected the request for the patent term extension citing former Commissioner Meir Noam’s ruling concerning Unipharm’s opposition to IL 90465 to A/S Lundbeck (3 February 2009), which ruled that the higher efficacy of enantiomer with respect to the racemic mixture was patent worthy, but did not provide a new material in the sense required for a basic patent that is eligible for patent term extensions.

On 24 November 2016, the Applicant appealed this decision to the Commissioner of Patents, reiterating the arguments that were rejected. Then Commissioner Asa Kling accepted that the enantiomer was not found in the racemic compound and agreed to a patent term extension of 959 days until 30 January 2023 (see ruling re IL 145996 to Takeda from 12 Feb 2017:

In paragraphs 24 to 26 of his decision, then Commissioner Kling stated:

I have been convinced that Lansoprazole is a compound of the enantiomers and it is not possible to isolate Dexlansoprazole from the racemic compound, in contradistinction to the state of affairs in Unipharm vs. Lundbeck where the racemic mixture could be separated into the enantiomers.

Where the relative efficacy is different, Applicants assertion that Lansoprazole is NOT a racemic mixture but rather that the enantiomers share the crystalline structure, one cannot isolate the R enantiomer.

Opposer’s Argument

On 25 May 2017, the Association of Israeli Industrialists opposed the ex-partes decision to issue a patent term extension, based on Section 64g(a) of the Israel Patent Law 1967 for the following reasons:

  • the registration in the register of medical formulations which was the basis for the patent term extension was not the first registration for the active ingredient, contrary to Section 6d(3) of the Law.
  • The Applicant concealed significant relevant facts from the Patent Office. So the Application for a Patent Term Extension is contaminated with inequitable behaviour and is contrary to Section 64b(1) of the Law.

These claims were supported by an expert opinion from Professor Menachem Kaftori dated 24 May 2017.

The Opposer relies on the Lundbeck ruling (Appeal 223/09 Lundbeck vs. Unipharm ltd from 25 May 2009 which asserted that the various terms for material in Section 64a include enantiomers, and wherever the material is an active ingredient or form of the active ingredient that is found in a prior medical formulation that is listed in the register, it cannot be considered as being a first registration under Section 64d(3) of the Law.

The Opposer further alleged that the applicant had already acknowledged that the active ingredient Dexlanoprazole is included in the racemic Lansoprazole in the pharmacology report for Kapidex in a request to market a formulation including Dexlansoprazole in the US (NDA 22,287) which was appended to the ex-partes submission.

Based on Professor Kaftori’s opinion, the Opposer further alleged that coupling between the different molecules in the crystal were inter-molecular bonds and not intra-molecular bonds, so that on dissolution into water a racemic mixture of the enantiomers results.

DexilantThe active ingredient of Dexilant™ is Dexlanoprazole and not the crystal, and the morphological structure of the crystal has no relevance to the issue of patent term extensions. The racemic compound is no different to a racemic mixture as has as the difference between its components, apart from the crystal structure of the raceme. The inclusivity of the re Lundbeck decision does not relate to the isolation of the material by separating the basic cell of the crystalline structure whilst in a solid state, but to the possibility of any separation.

The Opposer further argues that the efficacy of the enantiomers when considered separately or as part of the racemic mixture is not relevant to the question of whether the application in question relates to the first formulation that allows the material to be used for medical purposes in Israel.

LansopropazoleThe Opposer further claims that the Applicant concealed the fact that the material was previously registered in the Lansoprazole registration, and the experimental evidence used to justify the registration were those using Lansoprazole which the Applicant had asked to be relied upon. Similarly, the Applicant had concealed the fact that Lansoprazole had been defined by themselves as being a racemic mixture and not, as they now claimed, a racemic compound, for example, before the Canadian Federal Court of Appeal.

Applicant’s Argument

Takeda reiterated the arguments submitted in the ex-partes hearing by former Commissioner Kling, his ruling of 12 February 2017, and an Opinion of Professor Avi Bino of 19 September 2017.

Furthermore, Takeda rejected the allegation of inequitable behaviour noting that the racemic material Lansoprazole was disclosed and related to in their submission for a patent term extension, and reiterated that it was a different material.

optically active.jpegFurthermore, in their response of 28 August 2016, they clarified that Lansoprazole is racemic compound that is optically active in a different manner to that of the enantiomer. The XRay diffraction pattern of Dexlansoprazole is different, and it is a different chemical entity. The Applicant further claims that the request for a Patent Term Extension is based on a registered product and not on a material after subsequently undergoing any type of process within the human body [apparently dissolution is intended – MF].

The Applicant alleged that the Opposer did not provide support for the contradiction in Mitchell’s paper, and did not provide scientific textual support, experimental evidence or research to challenge the validity of the evidence submitted by themselves in the ex-partes proceeding.

In the pharmacology submission for Kapidex which includes Dexlansoprazole there was experimental evidence relating to pregnant women which included one test conducted with Dexlansoprazole and one test conducted with Lansoprazole. Thus contrary to Opposer’s assertion Dexlansoprazole was examined, and the testing of Lansoprazole was additional data.

Although the therapeutic results themselves are insufficient to prove that a patent term extension is justified, they do teach that there is a difference between the materials that allows a patent term extension.

raceme.jpgTakeda referred to the definitions of racemic mixture, raceme and racemic compound in the IUPAC gold book which is the definitions used by the International Union of Pure and Applied Chemistry and which they claim accords with Mitchell’s paper.

Finally, Takeda submits that the Commissioner is not able to sit in judgment and rule on a ‘kind of appeal’ of his own decision, or that of his predecessor.

Discussion and Ruling

For sake of clarity, the Commissioner notes that the term raceme relates to racemic mixtures of S and R molecules in equal amounts, or to racemic compounds where there is a repeating arrangement of the two enantiomers in different proportions within a crystal,

The legal authority of the Commissioner to rule on the Opposition

legalCommissioner Alon dismisses the allegation that he cannot hear this case. Section 64f of the Law allows anybody to oppose patent term extensions or their duration. Under section 64g, ANY reason that the Commissioner should not grant a patent term extension is a valid reason for opposing the extension. The right of the Opposer is independent of whether the extension was the result of an ex-partes ruling or otherwise.

The logic is clear. In the ex-partes hearing, one side presents THEIR arguments, evidence and documentation supporting the issuance of the PTE. The opposition is an adversarial proceeding whose purpose is to allow third parties to challenge the granting of the PTE, Once an Opposition is filed, the Commissioner is obliged to consider the issues raised and to reconsider the determination that a PTE is justified in light of the claims and evidence of the parties.

Registration of Lansoprazole allowed usage of Dexlansoprazole

Section 64d of the Law sets out the conditions for obtaining a Patent Term Extension. Inter alia, it states that one can only obtain an extension for a material listed in the pharmaceutical register, and only if that registration is the first registration of the material for medical use.

It does not appear that there is any dispute between the parties regarding the following facts:

  • The crystal of the Lansoprazole raceme is a racemic compound, which is difference from the enantiomer of Dexlansoprazole (Cross-examination of Professor Kaftori page 12 lines 12-18).
  • When the raceme Lansoprazole is in a crystalline form, one cannot separate the enantiomers into Dexlansoprazole and Levolansoprazole.
  • One can separate a solution of Lansoprazole into its enantiomers by known and established procedures for separating enantiomers. (Opinion of Professor Bino, paragraphs 13-14).
  • When Lansoprazole is separated into its enantiomers one obtains the R-enantiomer Dexlansoprazole and the S enantiomer Levolansoprazole.

As to the possibility of separating the enantiomers. Under cross-examination, Opposer’s expert Professor Bino agreed:

Attorney Tal Band:  Take, let’s repeat this, take a crystal of Lansoprazole, dissolve it in water and what do you get? I suppose you will allow me…

Professor Avi Bino: With pleasure

Adv. Band: You will obtain a solution that includes the R-enantiomer

Prof Bino: the R-enantiomer and the S enantiomer

Adv. Band: and the S enantiomer, which is the active ingredient if we now know that the active ingredient is the R enantiomer? It is the R enantiomer, right?  

Prof Bino: the R-enantiomer in solution

Adv. Band: the R enantiomer I solution is the active ingredient?

Prof Bino: Correct.

Protocol of 9 January 2018, page 53 lines 17-26.

In a different stage of the cross-examination, 9 January 2018, page 46 line 6:

Attorney Tal Band:  It can, that means to say, it can dissolve into the solution…

Professor Avi Bino: Yes

Adv. Band: And this change from crystalline to solution is not a chemical change but a physical one, correct?

Prof Bino: True.

Adv. Band: Good. So in the two states the chemical compound maintains its identity, correct?

Prof Bino: Correct.

See also paragraph 60 of the Applicant’s claims from 19 September 2017 and paragraphs 9-15 of Professor Bino’s Opinion.

right hand.pngThus there is no argument that the R-enantiomer included in Dexilant™ is the same R-enantiomer included in Lansoprazole.

In the Lundbeck ruling, the District Court ruled that registration of a raceme would be considered the first registration for the enantiomers.

The Applicant considers that the Lundbeck case is different since there one could separate the enantiomers as the patent covered a racemic mixture. However, in the present instance, one cannot separate the enantiomers whilst solid, but have to dissolve them in water first, and only then can the enantiomers be separated.

To clarify the point, the Applicant submitted the following schematic illustration on 28 August 2016 to the Deputy Chief Examiner:

Lansopropazole imageThe Applicant claims that the law relates to the active ingredient of the medical formulation, which is crystalline and so should be considered in this form.

lefty.jpgIn re Lundbeck, a mixture was considered, and the unit cell of r-enantiomer structure is found in the mixture (right side) and in the enantiomer (center top), whereas in the present case, (illustrated on the left), there is no r-enantiomer unit cell so one has to dissolve the crystal and then separate and recrystallize to obtain the separate enantiomers in crystalline form.

Applicant claims that the Law relates to the active ingredient of the medical formulation. The medical formulation includes the crystalline structure, and so it should be [examined for patent term extension purposes] in this manner.

The Examiner considers that the fact that one cannot separate the R and L enantiomers whilst crystalline is irrelevant. In paragraph 17 of the District Court ruling in re Lundbeck the court differentiates between inter- molecule bonds and intra-molecular bonds.

Even if we were to accept the Applicant’s claim that the Lansoprazole is a racemic molecule, there are no intra-molecular bonds, but only bonds connecting the molecules to each other, and each enantiomer molecule maintains its identity within the crystal. The attractive forces between the S and R molecules creates the crystal by inter molecular bonds (see paragraph 18 of Professor Kaftori’s opinion and Professor Bino’s remarks on page 48 lines 6-12 of the protocol. As Commissioner Alon clarifies below, it is incorrect to consider the material at the crystalline layer, and so the R-enantiomer is NOT to be considered a new material as far as Patent Term Extensions are concerned.

If one were to consider the crystalline form of the pharmaceutical formulation as being a new material as far as Patent Term Extensions are concerned, the consequence would be that one could dissolve Lansoprazole and consider the solution as being a pharmaceutical formulation, the solution contains both enantiomers in solution would be considered as a different formulation and thus subject to a Patent Term Extension, and it is difficult to accept this result.

Furthermore, the definition of material in Section 64a of the Law is:

“Material” – the active ingredient of the medical formulation or its salt, ester, hydrate or other crystalline structures of the same component.

Commissioner Alon considers that one should read Section 64a as all the forms of the active ingredient being considered the same material. This definition implies that the identity of the material is NOT considered in terms of its form in the formulation. The case-law has ruled that the fact that different enantiomers and crystalline structures have different physical properties does not make them considered as being different materials as far as patent term extensions (PTEs) are concerned – see District Court ruling in re Lundbeck, section 20.

This interpretation sits well with the rationale of the Law as stated in the Patent Term Extension ruling concerning IL 124123 to Bayer Healthcare LLC, 16 April 2018:

With regards to active chemical ingredients, one can claim that the legislator defined enantiomers that, although not structurally identical, can be considered as being the same active ingredient, since the experiments on the active ingredient will shorten the way or help develop drugs based on the same active ingredient. So different salts of the same active ingredient are defined as being the same active ingredient with respect to Section 64D(3) of the Law (it is noted that in other jurisdictions, a different conclusion was reached).

Additionally, there is an explicit connection between the breadth of patent protection under Section 64h(d) of the Law and the interpretation of the term ‘material’. Section 64h(d) states:

  1. d) If the Registrar granted an extension order, then the holder of the basic patent may – during the period in which the extension order is in effect – prevent any person from marketing or from producing in order to market without his permission the medical equipment or the medical preparation that incorporates the material, as far as the material, the process of its production, its use or the medical preparation or the process for its production were claimed in the claims for the basic patent.

Recognizing all forms of the active ingredient as being a new material as far as Patent Term Extensions are concerned would result in Patent Term Extensions being granted, not for all forms but only for the form of the active ingredient in the medical formulation. Commissioner Alon considers that proper policy is to provide wide protection for the party developing a new drug, and recognizing the physical form of the material as being different would result in narrowing the breadth of the patent term extension.

The Applicant argues that from the ruling of former Commissioner Noam regarding the Patent Term Extension for IL 97219 Novartis AG (26 December 2005) one can conclude that two active ingredients acting together could be considered as being a new material that is different from the two ingredients considered separately.

Commissioner Kling does not agree. In re Novartis, Commissioner Noam considered the eligibility for a Patent Term Extension for a formulation including two active ingredients that were previously separately recorded in the pharmaceutical register, and concluded that even were there to be a synergetic effect and not merely an additive effect (aggregation), this is only relevant for the question of patentability but not for the question of eligibility of Patent Term Extension, nothing further is stated.

It appears that Commissioner Kling’s ruling of 12 February 2017 was largely based on the conclusion that one cannot separate the enantiomers of the racemic compound. As shown in the Opposition by the statements of case and evidence, is that the compound can be separated into its enantiomers, and that the form is not significant. In other words, the factual basis for Commissioner Kling’s ruling has been eroded and we can thus change the decision.

In light of above, Commissioner Alon rules that the R enantiomer is found in Lansoprazole and the registration of Lansoprazole is the first registration of the R-enantiomer Dexlansoprazole which is the active ingredient of Dexilant™.

The Allegation of Inequitable Behaviour

The Opposer’s allegation that Takeda’s behavior was inequitable, contrary to Section 64b(1) of the Law, is supported by two props. One is the statement appended to the request for a patent term extension that was written by Miyuki Hora which states that Dexlansoprazole is the first registration that allows the use of the product for medical purposes in Israel, without going into details, which comes later.

In addition, the Oppose claims that the Applicant concealed the fact that the examination of the request for registration in the pharmaceutical formulation register relied on tests performed on Lansoprazole, and that the Applicant itself relates to Lansoprazole as being the racemic mixture in a proceeding before the Federal Court of Appeal in Canada, and regarding the date of the claim that Lansoprazole is a racemic compound.

The Applicant’s response to these claims was that the experiments were clearly indicated in the pharmacology report mentioned above, and Commissioner Kling even related to it in his ruling of 12 February 2017. As to the Canada decision, the Applicant acknowledges that they were inaccurate in their terminology regarding mixtures and compounds, but this was due to the fact that case related to a different issue and not to something relevant to the issue of whether the Lansoprazole raceme is a compound or mixture. The same inaccuracy is found in the FDA regulatory approval in the US.

When considering Miyuki Hora’s affidavit, it is true that it relates to the Lansoprazole raceme:

“… Although racemic Lansoprazole was previously approved for medical use, enantiomerically pure Dexlansoprazole has never been approved …”.

Additionally, it seems that the Applicant themselves muddled up the terms in the definition of the raceme, and sometimes referred to it as a mixture and sometimes as a compound, however the Commissioner does not consider that this is indicative of inequitable behaviour. Furthermore, in light of the above ruling, it is irrelevant whether we refer to the raceme as a mixture or a compound, since the question of whether the molecule were previously registered exists in the raceme, which we have established to be the case.

Conclusion

In light of the above, the Commissioner accepts the Opposition and cancels the patent term extension. The Applicant will pay 15000 Shekels costs and 100,000 Shekels legal fees to the Manufacturers Association of Israel.

Opposition by the Manufacturers Association of Israel  to Patent Term Extension for IL 145996 to Takeda, ruling by Commissioner Ofir Alon, 24 May 2018  

COMMENT

I think this decision is completely correct and is also well written and whilst comprehensively addressing the issues raised, is relatively concise.

Since the racemic compound dissolves into the free molecules, the discovery that the R-enantiomer is active may be inventive, but the clam that this is a new material that warrants a patent term extension is ludicrous in light of the previous cases related to by the Commissioner and linked to above.


Bayer – Part II – Are Patents for Bio-Similars Elligible for Patent Term Extensions???

June 5, 2018

This is the second part of a ruling concerning Patent Term Extensions (PTEs) for Kovaltry. The first part related to when the ninety day period from registration commences and is discussed here.

This second part of the ruling is a precedential decision that rules whether a patent for a bio-pharmaceutical material such as a protein can be can be considered as being a basic patent if there is a previously registered bio-similar molecule; it being appreciated that the amino acid sequence may be the same, but the spatial structure, activity and efficacy may still be different. In view of its legal and financial significance, the decision is fully translated below. We apologize for any incorrect technology. 

After the request for a patent term extension for Kovaltry was received from Bayer, the Patent Office issued an Office Action as follows:

Paragraph 6 of the Affidavit appended to the letter of 22 August 2017 notes that there is no other formulation that includes Recombination Human Coagulation Factor VIII, fabricated by the defined cell culture and the defined conditions under which KOVATLRY is manufactured. It is possible that the Blood Coagulation factor claimed in the Application is different from the Blood Coagulation Factors that have been registered, but the Active Ingredient of the Recombination Human Coagulation Factor VIII formulation is registered in the registry of pharmaceutical formulations in various formulations mentioned hereinabove.

The other medical formulations mentioned as including Factor VIII were Novoeight, Octanate 1000, Koate and Kogenate.

Kovaltry

On 11 December 2017, the Applicant responded to the Office Action and claimed that the active ingredient, the Recombinant Human Coagulation Factor VIII, is a new material derived from a new genetic engineering process that is protected in the present application, and that Kovaltry is the first formulation that allows its medical usage in Israel, as required for a patent term extension in Section 64D(3) of the Law.

The Applicant explained that Factor VIII is intended for treating Hemophilia A which is characterized by a problem with blood clotting due to a fault in or a lack of Factor VIII. In the new process covered by the Application, the heat shock protein 70 (HSP70) is introduced into the gene of the host cell and additional actions are taken to produce the active ingredient, which creates a new protein Factor VIII, which has a different structure from other proteins that relate to a lack of endogens in the Factor VIII coagulant. The structure of the protein, as applied for in the Application is as follows:

Bayer

The Applicant further explained that the folding structure of the protein is different due to the manufacturing route, and it attracts a lot of sugar groups (glycans), which allow the protein to automatically fold and provides a pharmokinetic advantage to the protein when compared to other formulations. In this regard, the Applicant notes that most properties, such as the glycan group appended, which have been glycosylated, are relevant to the half-life of the protein in the blood.

The Applicant claims that the registration file of the Kovaltry formulation indicates that the Ministry of Health considered the formulation to have a new active ingredient, and so it had to undergo the specific regulatory requirements of the Ministry of Health. The Applicant relies on the Procedure of the Ministry of Health for registering products of this type; Changes and Innovation in Medical Formulations from 1 February 2015, which differentiates between six different categories for registration.

According to the Applicant, when the Israel Ministry of Health relates to the Recombination Human Coagulation Factor VIII as being a new active ingredient as far as registration in the drug register is concerned, one has to apply a similar rationale when considering the drug for a patent term extension in order to fulfill the purpose of the legislation which is the underlining logic of the patent term extension, which is to compensate the patentee for the period when he cannot market the formulation containing the patented product due to regulatory requirements. The Applicant argues that one should differentiate between medical formulations that have active chemical ingredients that are small molecules, and biological formulations that are differentiated by proteins manufactured in different ways. They argue that the different proteins are typically different from each other in both their structure and their physical properties.

From the claims it transpires that the difference results from the way that the protein is manufactured. The applicant explained and supported their explanation with various appendices, the manufacture of a biological pharmaceutical formulation that includes proteins is very difficult due to the size of the protein, the way it folds, the general structure, changes in translating the chain of amino acids to create the protein, the cell culture used to manufacture the proteins, and so on. All changes lead to changes in the protein itself, in its. glycosylation and medical effect.

Due to these differences, the Applicant alleges that Health Ministries around the world have created different regulatory procedures for biological pharmaceutical formulations. They claim that even though there may be several medical formulations for addressing a lack of a particular enogen, such as Factor VIII, due to the issues raised above, they will be different from each other in practice. Furthermore, their active elements which cause blood clotting will be different and have different international classification.

In their response, the Applicant further explained that there are other formulations that treat Hemophilia A, which are fabricated in different ways such as by separating active ingredients from human plasma, formulations obtained by genetic engineering of part or a full gene, formulations that include healed proteins and formulations that include Factor VIII with additional proteins.  The Applicant claims that these formulations are completely different from Kovaltry, despite their purpose being to overcome the endogenic lack of the blood clotting Factor VIII as described above.

The Applicant focused on the differences between the active ingredients of the medical formulations cited by the Examiner and the active ingredient of Kovaltry. As to Kogenate, the Applicant claimed that its active ingredient was different to Factor VIII, even though the sequence of amino acids was the same, since the proteins of the structure are different at the gene level and the protein level. The Applicant appended journal articles that related to the differences between the formulations as an example of improved pharmakinetics.

In light of the above, the Applicant considers that one cannot apply Section 64D(3) of the Law in the same way for biopharmaceuticals when comparing active ingredients with prior art as is done for chemical pharmaceuticals.

In response to these claims, the Deputy Chief Examiner responded in a letter of 31 December 2017, that obtaining the strict regulatory approval required for pharmaceuticals is no indication that a patent term extension is also appropriate. To support this differentiation, the Deputy Chief Examiner referred to 223/09 H. Lundbeck A/S vs. Unipharm ltd et al (22 May 2009).

The letter also notes that the journal papers appended to the response explain that the process for obtaining Factor VIII in the patent in question creates a new protein with a different structure, with glycosylation and different pharmakinetic properties which affect the half-life of the protein in the blood, but do not influence the formulation, and the protein that is the active ingredient of Kovaltry is Factor VIII which exists in Kogenate and other pharmaceutical preparations.

Furthermore, the Deputy Chief Examiner considered that the improved glycosylation or the addition of the HPS70 may affect the folding and could be a new process, but the registration of a medical preparation is given for a formulation and not for the process of manufacture, and differences in the Factor VIII are simply a bi-product of the processing route.

The Deputy Chief Examiner added that though the process of manufacturing the proteins in Kovaltry and Kogenate are different with a difference that expresses itself in yield, better cells and other repeatability differences, the sequence of amino acids is the same, despite the amount of glycans that underwent glycosylation on the proteins So compared to preparations that were registered earlier than Kovaltry, the Deputy Chief Examiner rejected the Applicant’s claims with respect to each of the formulations.

On 7 February 2018, the Applicant submitted a request for a hearing regarding the rejection, and submitted a further statement of claims on 20 February 2018. O 25 February 2018 an ex-partes hearing was held before the Commissioner during which the Applicant reiterated their claims and added the following claims:

Factor VIII is a complex protein and changes in the process result in significant changes to the structure thereof and to the medical affect thereof. Consequently, when comparing twoproteins to ascertain whether or not they are the same material, one has to consider the structure and not merely the sequence of amino acids which is the first stage of characterization, but also the three dimensional form and the intracellular activity.

After the hearing, the Applicant submitted a summary on 1 March 2018 that proposed an appropriate test for considering the novelty of biopharmaceuticals. The proposed test has three levels. Firstly one should consider if the material is a biological medicine. Then one should consider if the protein has a new structure, and finally various tests for determining whether a protein is new or not, such as whether it is a specific protein, whether the regulatory approval was Read the rest of this entry »


When does the ninety day period for requesting a patent term extension commence?

May 29, 2018

Extension for IL 124123 to Bayer. When does the ninety day period for requesting a patent term extension commence?

In this ruling, the Commissioner accepts that the 90 day period for requesting a patent term extension should be calculated from the date at which the Ministry of Health informs the Applicant of the issuance of the decision to grant a patent term extension, and NOT from the date on the certificate. We now wait for someone to request that all sorts of cases be reopened, and extension fees refunded.

There is a second part to this ruling, in which the Commissioner rules on whether this is indeed the first registration of the drug. For blogging purposes, I am relating to the issues separately.

Kovaltry

The Application for the Extension for IL 124123 to Bayer was filed on 7 August 2016 and relates to the KOVALTRY formulation in the medical products registry from 8 May 2016, and which contains Recombinant Human Coagulation Factor VIII (no relation).

The Deputy Chief Examiner sent an Office Action on 13 September 2017 in which she raised the following objections:

  • The Application does not fulfill Section 64xv(a) of the Patent Law 1967 since it was received 9 days after the formulation was registered in the pharmaceutical registry.
  • The Application does not fulfill section 64d(3) of the Patent Law 1967, since it is not the first registration of Recombinant Human Coagulation Factor VIII in the pharmaceutical register.

The Applicant was also required to provide additional details regarding extension orders in the US and in recognized European countries.

On 11 December 2017, the Applicant responded to the Office Action. Following the Request for Patent term extension being rejected on 3 December 2017, the Applicant challenged the grounds for rejection. In their response, they submitted a detailed list of allegations on 7 February 2018 and a summary on 20 February 2018. The Applicant also attended a hearing on 25 February 2018. After the hearing on 1 March 2018 the Applicant submitted a completion of their case.

Bayer raised two main claims. The first was the way of calculating the timing of the request for the extension conducted by the Deputy Senior Examiner in accordance with Section 64xv(a) of the Law. The second related to the previous registration of bioactive ingredients for medical purposes in accordance with Section 64iv(3) of the Law.

Timeline for Submitting the Request for Patent Term Extension

When the Application was submitted on 7 August 2017, the Application wrote that “This Application based on the Kovaltry formulation that was registered on 8 May 2016, and so the Application is submitted within 90 days of registration.”

Ms Assem Mehta Deputy President, Head of the Department of Patents and Licenses, and Assistant to the Secretary, affirmed in an Affidavit supporting the request for patent term extension, dated 22 August 2016, noted in Section 4 of the Affidavit, that the medical device was registered on 8 May 2017.

However, from the Office Action, the Registration Date that appears on the Certificate of Registration is indeed 8 May 2017, but the request for the Patent Term Extension was only filed on 7 August 2017 which is 91 days from the registration date. Based on this data, the Deputy Chief Examiner ruled that the request does not conform to Section 64xv(a) of the Law which requires that:

Section 64xv(a)A request for a patent term extension should be submitted in the appropriate manner, after paying the fee, and not more than 90 days from registration in the Pharmaceutical Registry.

In the response to the Office Action from 11 December 2017, the Applicant claimed that although 8 May 2017 is the date at which the registration for marketing Kovaltry appears in the register, the Authorization only issued on 10 May 2017, and this was the date at which the Manager of the Register for Pharmaceutical Formulations informed the Patentees of the Approval. The Applicant appended a further Affidavit dated 14 January 2017, from Mr Gal Friedman, the Head of Regulation of Bayer Israel, which markets the Applicant’s products in Israel. In the Affidavit, Gal Friedman asserted that regulatory approval was only received on 10 May 2017. An email notification from the Head of Registration of Pharmaceutical Formulations, Dr Einbinder was appended. The email address was given as the formal electronic mailing address of Bayer Israel.

The Applicant claims that from their attempts to clarify the matter, that in the past, the date on the certificate was the only date available for calculating the 91 day period. However, nowadays, one can use the date of informing the Applicant as the starting period of the 90 days.

The Applicant claims that neither the Patent Law nor the Pharmacists Ordinance 1981 define the registration date that appears on the registration certificate. They thus allege that there is no basis to explaining that the 90 day period stated with this date is the correct date for calculating the 90 day period for requesting a patent term extension from a the Deputy Commissioner ruled, rather than the date at which the Applicant was informed (i.e. 10 May 2017).

The Applicant went on to claim that time periods for calculating things that depend on the Authority are generally to be calculated from when the citizen is made aware of the action of the Authority or when the notice is sent.

The Applicant wishes to draw a parallel to the C-471/14 Seattle Genetics from 6 October 2015, where it was ruled that the period for giving marketing approval under the European regulations, is from the day that the Applicant is informed, i.e. the date of notification. The Applicant claims that the basis for this determination is that the marketing approval does NOT enter into effect from the day that the decision is taken, but rather from the date that the Applicant is informed of the decision. Consequently, certificates of registration have two dates and the Applicant believes that one should prefer the later of the two, which fulfills the intention of the legislation, which is to provide a sufficient window for Applicants who have a basic patent, to request a patent term extension – something that they cannot do before knowing that a marketing approval has issued.

The Applicant alleges that this position is supported by the District Court ruling in 32321-10-16 Bristol Myers Squibb Holdings Ireland vs. Commissioner of Patents and Trademarks 26 December 2017, where Section 64x(2) of the Law was interpreted to mean that the period of marketing approval commences with the informing of the decision to the Applicant and not with the date that the Approval was made. The Applicant considers that this should apply to Section 64xv(a) of the Law as well.

The Applicant also considers that the explanation of the Law made by the Deputy Chief Examiner could result in many cases where the patent term extension period was determined by the date appearing on the certificate and the number of days would need to be recalculated.

DISCUSSION AND RULING

The issue in question is the correct explanation of the term “Day of Registration of the Medical Formulation” as mentioned in Section 64xv(a) of the Law.

In legislating that the Applicant should submit their request for a patent term extension within 90 days from registration in the Pharmacist’s Register, the legislators attempted to achieve two purposes:

  1. To give the Applicant sufficient time to prepare their application
  2. To allow the public to know with certainty whether a patent term extension was being sought for a particular product, thereby providing market certainty.

Section 64xv(a) has been amended. In the earlier version under the third amendment to the Law, the period for applying for a patent term extension was 60 days from registration of the formulation under the Pharmacist Regulations (formulations) 1986.

In the seventh amendment from 2006, 3 January 2006, Book of Laws 2048, page 195-197, the Section was amended to extend this period to 90 days. The Pharmacist’s Regulations were similarly amended and now state “from the day of recordal under the Pharmacist’s Ordinance. In the 11th amendment the Authority of the Commissioner to extend the period was taken away, so the period is non-extendible (Amendment 11, 2014, Law book 2430, 27 January 2014, pages 274, 278.

From the Applicant’s claims it transpires that there are four periods that could be considered the period of registration from which the 90 days are calculated:

  1. That given as the date of registration
  2. The day that the approval is printed on the certificate
  3. The date when the Pharmaceutical Division informs the owners of the registration – the sending date. and
  4. The date of knowledge – the day on which the owners of the registration receive notification of the registration.

The date of registration is that appearing on the certificate from which the ninety day period has traditionally been calculated when calculating the deadline for requesting a patent term extension (considering the certificate as it stands today).

The date of printing is presumably the date when the Ministry of Health produces the certificate. This is the date on page 3 of the Kovaltry certificate which states printed on 10 May 2017.

The claims and evidence before me do not support the contention that the date of printing of the certificate is necessarily the date on which the Ministry of Health informed the Applicant that their request for registration was successful. Indeed, one can assume that the date of printing will actually change each time that the same document is sent to the printer and so the same certificate could exist with different printing dates. Consequently, the Commissioner does not think that this date can be relied upon as the date for registration with regard to the correct explanation of Section 64xv(a) of the Law.

As to the period of sending or the period of becoming aware, the Commissioner accepts the Applicant’s allegation that calculating the deadline from the Official Date is problematic where the Applicant only becomes aware of the date retroactively, since it is difficult to require someone to take an action within a time period from an event occurring that he does not know about.

The issuance of a marketing authorization is an administrative action as defined in Section 3 of the Law of Interpretation:

An administrative action is an order or an appointment, notice, license, approval and the like, that is given in writing under Law and is not a legislative action.

In his book Administrative Authority, Y Zamir states that (Zamir, Administrative Authority Vol. 2 Second Edition, 201 on page 1320):

Common sense tells us that there are things where not being informed of an administrative decision that adversely affects a person’s rights, should not be in effect at all, or in certain circumstances, if the person was not informed of the decision. For example, let’s consider that an Administrative Authority cancels the work permit of a person but does not inform him of this, is it conceivable that the person will be tried under criminal law for running a business without a license? If an Authority applies a tax and does not tell him, can he be held liable for not paying that tax? Where a Law states that a person is allowed to Appeal or to critique an administrative ruling in some other way within a specific period from that decision issuing, and the person is not informed, should he be prohibited from criticizing the ruling? In summary, it appears that the present situation requires a legislative solution or case-law, that relates to publication of civil rulings. The underlining is by Commissioner.

Logic obliges that giving notification to someone regarding an administrative action relating to him cannot be applied without the person being aware of the administrative action. This is also stated in regulation 4 of the Patent Regulations 1968:

The calculation of the time period for doing an action the Law or regulations require or allow, following actions of the Commissioner or subsequent thereto, should enter into effect from the date when the requirement is given to the postal service and addressed to the client or agent-of-record at the official address, or sent by electronic mail, as per Regulation 16(b). This period starts with the sending of the electronic mail, unless it is established to the Commissioner’s satisfaction, that the message was not delivered.

True, in this instance, we are NOT talking about an action that the Patentee is required to take following an action of the Commissioner of Patents, but due to the action of a different Authority, the Ministry of Health, however the underlying logic is appropriate. It is noted that where the Pharmacists’ Regulations themselves give a time period for an action, the time period is from when the action of the Authority is made known to the person concerned, see, for example, Regulation 9(3) of the Pharmaceutical Ordinance:

 (b) If the director considers that the registration of the formulation in the register should not be renewed, he should inform the registered owner before the registration lapses, the notification should be by registered mail to the official address of the registered owner.  

(b1) If the manager informs that he does not intend renewing the registration, he should extend the registration by no more than six months.

(c) The owner of the registration is allowed to appeal the decision not to renew the registration within six months from receipt of the notification under Regulation (b).

So the patent regulations specifically state that where someone has to respond to an action of the Authority, the period for responding will be calculated from the day of sending or from the day of receipt of the notification if it is proven that the notification did not reach its destination. The pharmaceutical regulations state that the period is calculated from notification.

In the ruling of re Bristol, Judge Magen Altovia related to the “submission approach”.

 It is noted that the serving of papers approach sits well with the administrative law that stresses that the period of serving of papers is more important than the reaching of the administrative decision by the deciding party with respect to setting into practice that allowed.

As Judge Magen Altovia stated in re Bristol, the purpose of the civil law procedures is to fulfill real rights. See Appeal 6708/00 Aharon vs. Aharon p.d. 54(4) 702:

At the end of the day, the civil procedures are there to serve substantive rights, and they are there for a purpose. The wider substantive approach, of which good faith is the wellspring, cannot be accompanied by overly strict civil procedures. The legal culture is not only judged by protected rights, but also sometimes by the ways of approaching situations and the status of those being judged.

Consequently, Commissioner Ofir Alon considers that the 90 day period for requesting a patent term extension be calculated in a similar fashion to other deadlines in the Patent Law, i.e. in accordance with Regulation 4 of the regulations, that the date is to be calculated from when the notification is sent to the applicant / patentee, unless the Applicant can prove that the notice was never received, and in such cases, the period is to be calculated from when the consumer learned about the decision.

The Commissioner does not consider that calculating the period from the day that the Notice was given to the Applicant undermines the second purpose of the legislators; the need for certainty. This interest is not damaged if the date is calculated from the day of sending, since this is usually close to the day that the decision was taken by the Ministry of Health. It should be noted that Section 64 of the Patent Law has to be very carefully interpreted, to reflect the balances intended by the legislators.

In this instance, in the request for registration and in the affidavit, the Applicant noted the date of registration as 8 May 2018, even though Mr Friedman did not note that the notification was first sent to the Applicant on 10 May 2017, which the Commissioner is willing to assume was his intention in light of the Applicant’s claim, and noting the date of the printing appears on the certificate. In light of all of the above, the Commissioner rules that the response was timely filed under Section 64xv(a) of the Law.

COMMENT

This ruling seems to indicate that the Current Commissioner is less formulistic than his predecessors. I was rather taken aback by this ruling since I think that the 90 day period is ample to cover regular postage delays and his deadline should be no different from all the others that are calculated from the date on the certificate.

The Patent Office has very many deadlines triggered by an action they take, including the deadline for responding to Office Actions (typically 3 or 4 months, and extendible), the final deadline for responding to all Office Actions for registering a design (one year from the date of the first office action), the deadline for paying the first renewal (three months from issuance of the patent certificate), the deadline for filing oppositions, the deadline for filing abroad under Paris, etc. ALL of these calculate the deadline from the official date, despite the fact that, in practice, the Applicant will only be aware of the date once he/she receives notification which may be some time later.

The 90 day period is sufficient to cover delays of days in the authority informing the Applicant and the time for the Applicant to inform his client. If it can be shown that there were extraordinary delays involved, then there is due cause to argue that the delays were unavoidable and the Commissioner could reasonably give a discretionary extension. If the Law limits the grounds for discretionary extensions, it does so for good reason. In light of this ruling, ALL the deadlines triggered by Patent Office actions are now suspect.

There is no need for this. The 90 day period is sufficient to cover minor delays and, in this instance, the delay was three days. Sixty days used to be considered enough for filing a request. This period has been extended to ninety days. Ninety days is ample.

The 90 day period should not be extendible. The Law requires unavoidable delays and there was nothing unavoidable in this instance. However, although I think the ruling was horrible, there is a precedent for extending the 90 day period based on errors by agent of record being unavoidable. In XXXX, Reinhold Cohn missed the date due to docketing errors. If Pearl Cohen had claimed that they made a docketing error and calculated the date from receipt of notification, it is difficult to see how the present Commissioner could avoid giving the extension given to Reinhold Cohn. Of course, to do this requires knowledge of the previous decision which requires reading the decisions or following this blog.

Even without this, if the Commissioner simply ruled that the delay was unavoidable, he could simply have granted an extension based on payment of an extension fee. Instead, he has ruled that all deadlines are to be calculated from date of sending, or if not received, from date of notification. We predict that this will open a hornets’ nest.

Actually, there is a second issue here, which is whether this was the first publication. On that ground, discussed in the next blog posting, the extension was rejected. The Commissioner could, therefore, have ruled on that case and left the present issue open.


New Israel Patent Commissioner Makes Purpose Driven Interpretation of Patent Term Extension Legislation to Transfer Protection from One Drug to Another

December 21, 2017

Wyeth submitted a request for a patent term extension for Israel Patent Number 120701 titled “2 – PHENYL – 1 – [4 – (2 – AMINOETHOXY OR PROPOXY) ) – BENZYL] – INDOLE COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS CONTAINING THEM ” The patent issued on 26 December 2005 and the basic 20 year protection period will run out on 18 April 2019.

CONBRIZAOn 17 June 2012 Conbriza was registered in the Israel register of drugs. Conbriza contains bazedoxifene acetate. This was the first Israeli registration of Bazedoxifene for medicinal purposes and so, on 19 October 2015, a patent term extension order issued for Conbriza, until 14 April 2022.

DuaviveOn 16 November 2016, the drug Duavive which contains bazedoxifene acetate together with conjugated estrogens was registered in the Israeli register. The Applicant explained that Duavive is a more modern version of Conbriza which Pfizer (which owns Wyeth) had developed and is marketing in Israel.

The treatments are both for treating the symptoms suffered during menopause, such as the so-called hot flushes.

calculation

On 22 May 2017, the Wyeth informed the patent office that Conbriza was taken off the drug register and Duavive was registered. Wyeth claimed that the change should not affect the patent term extension since both drugs contained bazedoxifene, and that the patent term extension should be calculated from the first of the registrations.

Following this notification, the Applicant was invited to attend a hearing under section 149 before a ruling issued. The Applicant did want to attend such a hearing and on 5 July 2017 the Commissioner Ophir Alon indicated that in the hearing, which was held on 31 July 2017, the Applicant would explain why they felt that the provisions of Section 64(vii)(3) should not apply in this case.

Ruling

Section ii(1) of Chapter D of the Law deals with patent term extensions. Inter alia, Section 64D of the Law states that:

64D. The Registrar shall not grant an extension order, unless the following conditions have been met:

(1) The material, the process for its production or its use, or the medical preparation that incorporates it or the medical equipment was claimed in the basic patent and the basic patent remains in effect;

(2) In respect of a medical preparation—a medical preparation that incorporates the material is registered in the Register of Medical Preparations under regulation 2 of the Pharmacists Regulations (Medical Preparations) 5746—1986 (hereafter: Pharmacists Regulations);

(3) The registration said in paragraph (2) is the first registration that allows the material to be used in Israel for medical purposes;

(4) No extension order was granted previously in respect of the basic patent or in respect of the material.

From here, it is clear that the condition for giving a patent term extension is that there is a registration of a drug that includes the active ingredient and it is the first registration that allows the active ingredient to be prescribed in Israel, which was not previously subject to a patent term extension.

Section 64L states the cases where a patent term extension lapses. In 64L(3) it is stated that:

64L. An extension order shall laps in each of the following instances:

(3) If registration of the medical preparation that incorporates the material was cancelled—on the day on which the registration was cancelled;

Thus the wording of the black letter law seems to be that if the registration including the active ingredient is cancelled, the Patent Term Extension is cancelled as well.

The Applicant’s claim is that in cases where the company that registered the first drug has a number of registrations for different drugs containing the active ingredient, the Legislators did not intend that the protection period would lapse simply because one of these was cancelled. Rather, the legislators intended that only in cases where at some time after the issuance of the extension period, there are no registrations of drugs including the active ingredient in Israel, the extension period would lapse. In such an instance, where there are no drugs on sale in Israel there is no legitimacy in keeping the patent term extension active and so Section 64L(3) applies.

The Applicant claims that since Duavive contains the active ingredient and was registered before the registration of Condiza was cancelled, one or other preparation containing the active ingredient was continuously registered in Israel and so the patent term extension remains in force.

The Purpose of the Patent Term Extension Regime

As known, the term of a patent is 20 years from filing in Israel [or from the PCT filing date – MF] subject to paying extension fees. This period is the accepted balance between the desire to encourage inventors on one hand, and to enable the population to benefit from technological advances on the other.

balance

This balance has a special regime for pharmaceuticals and medical devices that is given by Section B1 of Chapter 4 of the Law. This regime compensates patentees for delays in registration but allows the generic drug industry to prepare for market entry to the benefit of the population as a whole. Where the conditions of the Law are met, it is possible to extend patents for pharmaceuticals and medical devices by up to five years.

This is how things were presented on page 18 of Appeal 8127/15 Israel Association of Industrialists vs. Mercke Sharpe and Dohme Corp, 15 June 2016:

The purpose of the extension period is to compensate the patentee for the period of patent protection that is de facto lost due to the amendment of the patent law. The period of protection in Israel and other countries having patent term extensions takes into account the period that the patentee takes to register the drug which is longer than the period lost by the patentee. However, in the Draft Amendment by the Committee for Constitution, Law and Justice it is stated that the extension is for the period that the patent for the drug is registered but regulatory approval by the Ministry of Health has not yet occurred, and so the extension is identical to this period. Either way, the main purpose is to provide fair compensation to the patentee.

Explaining section 64L(3)

As stated previously, there are two possible interpretations to Section 64L(3) of the Law. In the first explanation the words “registration of the medical preparation that incorporates the material was cancelled” relates only to the first registration, as defined in Section 64D(2), so that when the first registration is cancelled, the patent term extension ends.

The second explanation, proposed by the Applicant, is that one should understand the words “registration of the medical preparation that incorporates the material was cancelled “ as relating to all drugs that include the active ingredient and not merely the first one to be registered, so that there are no drugs including the active ingredient on the register.

Ofir Alon

The New Commissioner Ophir Alon considers that the interpretation is in line with the rationale of the Law proposed by the Applicant. As stated previously, the intention of the legislator was to compensate the patentee for the period required to register the drug. Section 64D of the law refers to the conditions for granting a patent term extension. The purpose of 64D(2) of the Law is to ensure that the active ingredient has undergone registration, and that of 64D(3) to ensure that that this was the first instance of the active ingredient being registered.

Since these conditions are fulfilled, it does not seem that there is much significance in the first registration specifically, that its cancellation requires cancellation of the patent term extension and cancelling the compensation that the law provides the patentee, whilst the active material remains registered, albeit with other active ingredients.

Registration of more advanced or better drugs that include these active ingredients is desirable.  Such registration is likely to require additional registration by the Ministry of Health. Adopting an interpretation under which the cancellation of the first registration for which the patent term extension period was calculated automatically results in the cancellation of the patent term extension will lead to a situation in which the patentee who has several registrations will have to keep the registration of a drug not being sold in force merely to keep the patent extension in force. This is artificial and not desirable.

However, accepting the second interpretation allows the patentee to cancel or not renew the first registration whilst keeping the patent term extension in place to protect additional drugs subsequently registered. This prevents circumstances where a patent term extension is in place but no drugs are registered for sale in Israel.

In summary, it appears that the correct interpretation of the Law is to compensate the patentee for the period he could not exploit his patent whilst waiting for regulatory approval, which includes protecting the public interest by promoting development of new treatments, and these aims are achieved by the interpretation allowing the extension to stay in force as long as there are drugs that include the active ingredient.

This interpretation serves the purpose of the Law and the public interest as it provides an incentive for the patentee to develop new versions of its drugs, that are more advanced or more efficacious than the original treatment, and allows the cancellation of registrations that are n longer marketed.

The Commissioner is aware that linguistically, the objective pronoun “the medical preparation” apparently relates to the medical preparation mentioned previously. Nevertheless he does not think that a literal reading helps to clarify things in this instance. For example, if we were to take a literalist approach to understanding section 65L(3) we would wonder what the legislator intended by “including the ingredient” at the end of the section, since it is clear that the medical preparation whose registration was the basis of the patent term extension includes the active ingredient, as stated in Section 64D(2):

(2) in respect of a medical preparation—a medical preparation that incorporates the material is registered in the Register of Medical Preparations under regulation 2 of the Pharmacists Regulations (Medical Preparations) 5746—1986 (hereafter: Pharmacists Regulations);

FROM THE GENERAL TO THE SPECIFIC

The cancellation of the Conbriza registration occurred after Duavive was registered, and so in one form or another the active ingredient was continuously registered from when Conbriza was registered until today.

So, by applying a purpose-driven interpretation to Section 64L(3), the registration was never cancelled and from when the patent term extension was issued until today, the medical preparation was under continuous protection.

The medical preparation Duavive includes the bazedoxifene ingredient together with conjugated estrogens. In other words, to create continuity in the registration, the active ingredient has to be identical to the one for which registration was granted. The Patent Term Extension for Israel Patent No. IL 120701 will remain in force subject to the Applicant submitting an Affidavit that the combination of the bazedoxifene ingredient together with the conjugated estrogens does not create a new material. This affidavit must be submitted within 30 days of this ruling.

Ruling concerning the Patent Term Extension for Israel Patent No. IL 120701 for bazedoxifene (Conbriza and Duavive), Ophir Alon, 15 October 2017

COMMENT

This ruling could be a baptism of fire for the new Commissioner.

The main question that the appointment of a new commissioner generates is whether he will favour the drug development industry or the genetic drug industry. The sums of money generated every day of a patent term extension and in supplementary patent protection for variants such as changes in dosage regimes is enormous. In this regard, Israeli companies are involved as both generic players and as drug developers. Despite TEVA being the world’s most successful generic drug provider, It was Teva’s Copaxone falling over the so-called patent cliff that caused the massive drop in share prices and layoffs, rather than lost sales of generics.

Here the Commissioner has taken an analytical approach to the law, trying to understand the rationale rather than the most literal interpretation. This is in line with guidelines penned by Former Chief Justice Aharon Barak who was known for such interpretations, which perhaps less charitably and more formalistically could be described as subverting the Law as legislated to further lofty aims as he saw them. Such creative interpretations coupled with him declaring that Basic Laws were constitutional and reading into them powers that the Knesset never intended, has led to judicial activism that those on the right see as undermining the Knesset as legislator, and those on the left see as saving democracy from the people’s elected representatives.

I remember litigators that represent the drug developing companies saying during Dr Meir Noam’s term as Commissioner, that, until he was replaced, their clients could not get justice. I do not know if this was fair. Dr Noam was a chemist, and generally where he accepted Unipharm’s arguments that an opposed patent application lacked novelty or inventive step, their arguments were persuasive, or at least seemed so to me. Nevertheless, in practice, he did rule in favour of the generic companies, but his rulings held up on Appeal.

At the start of his term in office, the previous Commissioner, Adv. Asa Kling, could not rule on cases where one side was represented by Reinhold Cohn or Gilat Bareket because of a perceived conflict of interest. Centocor Ortho Biotech Inc. received regulatory approval for a pharmaceutical preparation described in IL 154325.

From the affidavits submitted by employees of the agents for applicant (Reinhold Cohn Patent Attorneys) it is clear that, despite the firm being organized and having procedures in place to cover patent term extensions, there was human error. The deadline was missed and this was discovered seven months later.

Section 164 A1 of the patent law states that:

164.—(a) The Registrar may, if he sees reasonable cause for doing so, extend any time prescribed by this Law or by regulations under it for the performance of anything at the Office or before the Registrar, except for…section 64… …unless he is satisfied that the application in Israel was not submitted on time because of circumstances over which the applicant and his representative had no control and which could not be prevented;

The Deputy Commissioner Jacqueline Bracha threw Reinhold Cohn a life-line by ruling that mistakes were unavoidable, thereby allowing a missed deadline for requesting patent term extensions to be retroactively extended despite the Law being unequivocal that the deadline was not extendible. For more details, see here.

The patent term extension legislation has been amended several times, in the third, seventh and eleventh amendments to the Israel Patent Law.

The third amendment was ambiguous and in an ex-partes ruling affecting three patents in what is now known as the Novartis ruling, Then Acting Commissioner Israel Axelrod understood that the amendment was designed to give a real advantage to the drug development companies and they could choose the country to base their patent term extension on.  This was not what the Knesset intended and the amendment was again amended in what was the Seventh Amendment of the Israel Patent Law, to tidy up this and other ambiguities of the original amendment. Israel Axelrod, who was widely expected to be appointed as Commissioner but instead, was side-ways promoted to the Beer Sheva District Court.

In 2006, under intense pressure from the US who put Israel on their special 301 Watch List of countries not properly protecting Intellectual Property, the State of Israel amended their Patent Law again.

Arguably the Commissioner is correct that the purpose of the Law is to strike a balance between the conflicting interests. Arguably, however, as in the Novartis ruling and subsequent amendment, the intention of the legislators remains to provide narrowest possible intention to rules governing patent term extensions, to encourage generic competition, thereby favoring local industry over foreign companies, and providing cheap medicine. We should bear in mind that the legislation was the result of heavy US protectionist pressure, and in the same way that the US government tries to benefit US interests, it is (at least arguably) legitimate that the Israel Law is intended to protect local interests as much as possible.

Teva is not, of course, the only Israel company to bring a drug to market. Neurim managed to patent Circadine which is a treatment for insomnia based on melatonin, and also obtained patent term extensions around the world. In the UK, the patent office refused to grand a patent term extension arguing that the active ingredient was used in a treatment for sheep.  Judge Arnold upheld the patent office’s position, see patent term extensions for Neurim which was appealed to the House of Lords, and Lord Robin Jacobs referred it to the European Court of Justice ECJ in his last ruling on the bench. The ECJ took a similar position to that of the current commissioner, preferring an interpretation that considers the rationale behind the law to a literalist ruling.

The main problem with ex-partes rulings is that arguments of the other side are not heard.  It is not inconceivable that Duavive works and Conbriza didn’t, not because of a new material being developed but because of some symbiotic effect between the bazedoxifene ingredient and the conjugated estrogens. In this instance, Duavive was developed by Wyeth/Pfizer but it is not inconceivable that such a drug could be developed by a third party. If the Conbriza formulation is not on sale and no other drug by the patentee, should Wyeth-Pfizer be entitled to a drug term extension past the main patent lapsing? Another hypothetic question worth considering is that an active ingredient protected by a patent term extension could actually not be so active at all, and could be co-dispensed with a drug that itself is active, but cannot be patented. The combination could be protected by the patent term extension in a scam designed to defraud the public. I am not alleging that this is the case here. I have no ideas what conjugated estrogens do or how they work. I am merely highlighting a slight logical flaw in the Commissioner’s reasoning.

That as may be, this ruling is a brave but reasonable one. Being ex-partes it cannot be challenged directly, but could be challenged by TEVA, Unipharm or some other generic company launching a Bazedoxifene containing formulation during the extension period.  The Knesset could also decide to amend the Patent Extension Law to rule out this interpretation if they deem fit to do so.


Extension of Israel Patent Extended

June 8, 2017

BSSIsrael Patent No. 164987 to Bristol-Myers  Squibb is titled ” PROLINE DERIVATIVES AND  PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME”. On 9 January 2017, the relevant Examiner calculated that the patent was entitled to a 479 day extension. The patentee has appealed this calculation.

The patentee’s representative submitted his calculation and a hearing was held on 28 May 2017. Following the hearing, the Deputy Commissioner accepted the arguments and ruled that the extension should be 679 days.

SunvepraThe patent term extension is for the active ingredient of Sunvepra which is asunaprevir. The Application for a patent term extension was under section 64(o) of the Israel Patent Law. The Applicant notes that the drug is not marketed in any of the relevant States as per section 64(a) and so the period of protection should be calculated on the basis of Section 64(i)(b) as follows:

If the registration is only requested in Israel, the patent term extension will be in force for a period equivalent to that from when the request for registration was submitted to when approval occurred, so long as the Applicant acted equitably and with appropriate efficiency.

The disagreement between the Examiner and the Applicant concerns the proper interpretation of the term approval as used to indicate the period of the extension. There is consensus that this period starts with the submission for regulatory approval, but the end of this period is disputed. The Examiner considered that this period terminates with the registration of the medication in the register of medical formulations as per section 47a of the Pharmaceutical Ordinance 1981. The patentee contends that the date should be the date on which approval for sale of the drug occurs.

In accordance with Section 64a of the Law, the term approval is defined in section (b)1 of the Law in the same manner as in section 54a as follows:

In this Section, ‘approval’ is authorization or permission or other document needed to sell the product.

The Legislative was aware of the difference between the term רישוי meaning approval and רישום meaning registration. The term רישום (registration) is used in sections 64(d)2 and 64(d)3. The meaning of the term רישום (registration) is registration in the Register of Medical Formulations under section 47a of the the Pharmaceutical Ordinance.

The term רישוי (approval) used by the legislative for calculating patent term extensions is wider and includes all approvals needed to market the product. Where the product is a medical device there is no disagreement that after registration in the register there are other approvals necessary before a product can be marketed to the public. These approvals are listed in regulations 14-18 of the Regulations or Pharmacists (formulations) 1986 and we are concerned with the first of these in regulation 14:

No one may market a formulation for the first time in Israel unless it is from a batch that receives marketing approval from the manager.

The Examiner himself was aware that to marketing approval was required in addition to registration as is clear from his letter of 6 September 2016. There is no doubt that this marketing approval was only signed on 4 September 2016 as is clear from the appendix to the Affidavit of Ms Talya Ben-David, Brostol-Myer Squibb’s regulatory manager in Israel. So although the formulation was registered from 18 February 2016, it was only approved for marketing some 200 days later.

The Applicant’s understanding of the Law is ‘technical’. As is clear from the Appeal to the Jerusalem District Court 223/09 Lundbeck vs. Unipharm (25 May 2009) regarding understanding terminology of the Law:

One can therefore say that the substantive scope of considerations that the Commissioner may use when determining the period of protection is different from that when considering a patent application. Deciding whether an invention is patentable is by nature discretionary in that it requires ascertaining novelty, inventiveness, utility, etc. In contradistinction, when determining the appropriate patent term extension, the Commissioner is limited to considering the formal requirements of the Law, without consideration of the way the invention works or the Applicant’s investment in inventing, developing and registering. This is what the legislative body decided was the appropriate way to balance the conflicting interests when providing patent term extensions. The burden on the Commissioner is technical and is designed to be objective.

It so happens that this technical calculation also corresponds to the purpose of the Law which is to compensate the Applicant for regulatory delays whilst enabling competitors to test and develop their generic equivalents without infringing the patent.

Section 54a of the Law, legislated as an amendment to the 1967 Law, cancels the de facto extension of products requiring approval (particularly drugs), by enabling generic competitors to prepare for and obtain regulatory approval whilst the patent is in force and to launch their products immediately on the patent lapsing. In compensation for this change, the patentees were allowed to obtain patent term extensions. The extension is not for the whole patent but only prevents manufacturing and sale of the medical formulation that includes the material covered by the patent (Section 64(h)d of the Law). Just as the de facto extension for regulatory approval is needed to market the drugs, so the compensation for the drug developers, by enabling patent term extensions, is tied to approvals. The patent term extension is needed to compensate the patentees for “the period that has passed until the patentee receives approval from the Israel Office”. See also the words of explanation for the fourth amendment to the Patent Law (use and patent term extension) 1997, Draft Law 2664 page 146 onwards.

Although the Israel Law is not identical to the arrangements reached in the US and in Europe, it seems that there also, the patent term extension is calculated from the time that all approvals are received. See for example Section 14 of the Medical REGULATION (EC) No 469/2009 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL   concerning the supplementary protection certificate for medicinal products of 6 May 2009:

“The certificate shall take effect at the end of the lawful term of the basic patent for a period equal to the period which elapsed between the date on which the application for a basic patent was lodged and the date of the first authorisation to place the product on the market in the Community, reduced by a period of five years.”

See also 35 USC 156 which deals with determining the “regulatory review period for the approved product” and also the words of explanation for the 13th amendment of the Patent Law 2012:

“The approval of the extension period for patents for medical formulations and medical devices of the type given in the US (Patent Term Extensions PTE) under Section 156 of Volume 35 of the US Code. This approval extends the US patent for delays in obtaining regulatory approval for marketing medical formulations and medical devices that occur after the patent issues, and half of the period for clinical trials for the same medical formulations and medical devices, with deductions from this period for tardiness by the patentee in obtaining such regulatory approval. The period of the Approval given in the US under the US Law cannot exceed five years and cannot extend beyond fourteen years from the first marketing approval of that medical formulation or medical device.

However, reference to foreign laws is not required since the term ‘approval’ in Section 64(i)2 is clear and unambiguous:.

The proceeding for considering the request for a patent term extension

extension

Section 64(o)b provides a very short period for examining requests for patent term extensions. This short period obligates fast examination and does not allow back and forth exchanges between the Examiner and the Applicant.

The examination of the patent term extension request commenced on 6 September 2016. In an Office Action the Examiner explained that the Application did not accord with Section 64(d)(3) of the Law since at the time of the Application, there was no regulatory approval in Israel, so he considered that the registration did not allow the formulation to be legally marketed.

The Applicant challenged this ruling before the Commissioner but this before this was substantively considered, an Affidavit was submitted that showed that marketing approval was given on 4 September 2016 and so the Commissioner ordered the request to be examined.

On 8 January 2017 the Examiner informed the Applicant that the Commissioner was willing to give a 783 day extension, and gave him a month to relate to this. The method of calculation was not detailed.

calculationThe following day, on 9 January 2017, the Applicant requested details of this calculation and established telephone contact with the Examiner. The contents of the conversation were not documented but the Applicant’s representative explained the main points discussed. [why the Examiner wasn’t interviewed is not discussed]. In the discussion, it was noted that an error had occurred in calculating the extension period which did not conform with either the Applicant’s or the Examiner’s interpretation of the Law. The Examiner considered that the extension period should be from when regulatory approval was requested until registration of the product. Consequently, that day, 9 January 2017, the Examiner issued a letter correcting the 783 days to 479 days, commencing on 27 October 2014, when regulatory approval was sought, and ending on 18 February 2016 when registration occurred. Due to an error, the Applicant was not given a month to appeal this decision. Instead, it was published in the January 2017 patent journal. Thus on 31 January 2017, a notice that an extension would be given under Section 64(e)c of the Law, despite the Applicant appealing the decision on 22 January 2017. It is emphasized that Section 64(e)c of the Law allows the Commissioner to publish the announcement within 60 days, thereby allowing the Applicant to appeal the examiner’s decision prior to it publishing, which is his right under section 161 of the Law.

There is no doubt that the publication is an error that should be corrected under Section 170 of the Law. The error is twofold: Firstly, it should not have published before the Applicants appeal was heard. Secondly, the publication did not accord with Section 64(i)b of the Law, as clarified in this ruling.

Therefore, a new announcement will publish in the June 2017 journal to the effect that the patent term extension is 679 days. Under section 170(c) the public may oppose this correction.

Ruling by Deputy Commissioner Bracha regarding Patent Term Extension to IL 164987.

COMMENT

I found this ruling convincing and concur that it seems to fit with the intent of the Law and not just with its literal wording. However, the corrected calculation may be opposed both substantively based on alternative interpretations and also due to third parties relying on the shortened term. We await further developments.

 

  

 

 


Extending the Deadline to File Complaint

September 13, 2016

genentechIL 146954 to Genentech is titled “HUMANIZED ANTI-ErbB2 ANTIBODIES AND TREATMENT WITH ANTI-ErbB2 ANTIBODIES”. It is the national phase of PCT/US2000/07366. The active ingredient is Pertezumab.

Pertuzumab received US FDA approval for the treatment of HER2-positive metastatic breast cancer on June 8, 2012.[3] Pertuzumab was developed at Genentech and is now owned by Roche which acquired Genentech in 2009. The drug received regulatory approval in Israel on 8 July 2012, and on 21 February 2013 a patent term extension was requested and this was granted until 11 May 2021.

patent-extensionThe patentee requested an extension of time for responding to an Examiner’s action under Section 161 of the Israel Patent Law 1967. As explained below, the intended response relates to the intention to publish the grant of a patent term extension until the date awarded. However, the intention published in the July 2016 journal.

On 19 February 2013 the patentee requested a patent term extension for IL 146954. The conditions set out in Section 64e(5) of the Law were in place, but at that stage there was no extension to the basic patent in the US as required by 64d(5).  In the January 2015 journal there was an announcement of the intention to grant an extension under Section 64e(5) 1 of the Law.

Afterwards, when the Section 64d(5) requirement was met, the patentee gave evidence of the patent term extension of the basic patent in the US. In that notice the patentee noted that they expected that the Examination would be completed and a corresponding extension of the patent would be granted.

Consequently, the Deputy Senior Examiner completed her Examination and, on 4 July 2016, informed the patentee that the patent was entitled to a 353 day extension until 10 June 2021, which is the length of the extension in the US, and is the shortest of all the extensions granted by an extension granting state, as per Section 64i(1) of the Law.  The Patentee had until 18 July 2016 to respond to this notification.

calculating-sec-154-patent-term-adjustments-1-728-1On 18 July 2016, the patentee responded to this notification. From the wording of the response it is clear that the patentee does not have any problem with the mathematics used in  calculating the patent term extension. However, the patentee noted their position that the Examiner should take into consideration not just the Patent Term Extension period in the US (PTE), but also the Patent Term Adjustment (PTA) in the US.

Without substantive reference to the relevancy or otherwise of the Patent Term Adjustment, it is noted that until the patentee requested that the extension NOT be published, Genentech (Roche) had not raised Patent Term Adjustment (PTA) related issues and even now, did not provide details of the Patent Term Adjustment granted by the USPTO. So the Examiner was under no obligation to relate to this additional time period.

Once the period for responding had passed, and on receipt of the Patentee’s response, the Examiner informed the Patentee on 18 July 2016 that she intended extending the patent protection period in  Israel by the Patent Term Extension (PTE) awarded in the US as per Section 65(e)(5)(3) and that this decision would publish for opposition purposes in the July Journal, and this happened. The request to extend the period for filing a critique was submitted on 11 August 2016, after the publication of the extension order. The contents of the critique, which has not been submitted, is unknown.

The reason put forwards by the patentee for the patent extension is based on the allegation that the current law damages their property rights and they are considering the possibility of changing the current legislation. Thus it follows that the patentee does not contend that the Examiner’s actions were in accordance with current legislation. The requested Extension is until the basic patent lapses, which is until 23 June 2020, or a further year if the Patent Term Extension is also considered.

Thus the patentee does not argue that the Examiner was acting in contravention of the law and admits that the Examiner’s actions were in accordance with current legislation. The Commissioner, Asa Kling, does not believe that a patentee’s intention to try to change the legislation is sufficient reason for the Israel Patent Office to delay publishing its actions; particularly when the action has already happened and happened in accordance with the Law.

So the Commissioner does not see fit to extend the period prior to publication.

In a footnote, the Commissioner does not think that his refusal in any way adversely affects the patentee, since he can always submit a detailed request for recalculation under Section 164(c) of the Law.

COMMENT

In a recent decision the Supreme Court weighed in on a challenge to the patent term extension rules as being unconstitutional, and found that the legislative body can write the rules as it sees fit, to find  a balance between the competing need of the drug developers to be able to profit from their investment and have an incentive to conduct research and development and to file applications, with the public good provided by competition, non-monopolistic markets with generic competition.

The specific issue of the differences in Patent Perm Extensions and Patent Term Adjustments was discussed in a February decision.

I can understand the drug manufacturers considering the current law unfair, but, in light of the amendment to the amendment, it does seem to reflect what the Knesset wants and has been upheld by the courts. I don’t think that Genentech – Roche will be able to  have the Law changed.


Reconsideration of a Patent Extension Term

August 10, 2016

last minute shopping

In an odd development, but not one that without precedent – see here and here – Dr Shlomo Cohen Law Offices has asked the Israel Patent Office to reconsider a judicial ruling.

In this instance, the original ruling relates to the Patent Term Extension (PTE) of IL 169693 to “Bristol Myers Squibb” and Pfizer that issued under section 64(v)5 of the Israel Patent Law. The original ruling issued in September 2015, and granted a patent term extension of 974 days until 18 May 2025. That ruling followed a challenge by the patentees to Examiner’s decision of 5 March 2015.

The way that Patent Term Extensions (PTEs) are calculated in Israel is detailed in Read the rest of this entry »