Israel Patent Application No. 174082 to Novartis is titled “METHANESULFONATE SALT OF N – PHENYL – 2 – PYRIMIDINEAMINE DERIVATIVE, PROCESS FOR ITS PREPARATION AND USE THEREOF FOR THE PREPARATION OF A TABLET CONTAINING THE SAME”.
On allowance, Teva Opposed the patent. This decision relates to the utility requirements and to double patenting.
The Israel Application is a divisional application of IL 133906 which is a national phase entry of PCT/EP1998/004427, claims priority from a Swiss application filed back in 2007. The case published as allowed at the end of May 2010, and an Opposition was filed by Teva on 28 August 2010.
Following Statements of Case from the parties, Novartis submitted a request to correct the claims, and narrowed the scope of claim 1, adding a dependent claim 2. This somewhat delayed the proceedings. In May 2012, the Applicant requested a further amendment to narrow the scope of claim 1. (During Opposition, and indeed after grant, claims may be narrowed, so long as doing so is clearly a narrowing in all cases).
Teva did not object to either amendments and submitted an amended statement of case in June 2013. Novartis responded in September 2013 and by November 2014 both sides had submitted their evidence.
Teva submitted an expert opinion by Dr. Mark Zakrzewski and Novartis filed expert opinions from Dr. Simon Bates and from Patent Attorney Dr. Gail Volman. However, in lieu of a hearing, the parties agreed that the Commissioner would rule on the case based on the submissions, and, following his agreement to so doing, the parties filed their summary statements and counter statements.
The subject matter of the patent is Imatinib (N-phenyl-2- pyrimidine-amine) which was developed in Ciba Geigy, later Novartis, and is marketed as Gleevec® in the U.S. or Glivec® in some other countries. It is a competitive tyrosine-kinase inhibitor used in the treatment of some types of cancers, most notably Philadelphia chromosome-positive (Ph+) chronic myelogenous leukemia (CML).
(An opposition was lodged against the application in India by several Indian generic drug manufacturers including NATCO Pharma Ltd., CIPLA Ltd. Ranbaxy Laboratories Ltd., Hetro Drugs Ltd. and also by the Cancer Patients Aid Association. On April 1st, 2013 the Supreme Court of India dismissed Novartis’ patent application, so there are generic versions of the drug on the market. in India and the majority of the patients – 300,000 patients – are treated by the generic versions).
In Glivec, the Imatinib Methanesulfonate is found in the Beta polymorph which differs from the needle-like alpha polymorph and this affects various physical properties.
After the amendments described above, the claim set consisted of five claims, the first being independent. The main claim is directed to non-needle-shaped crystals having certain diffraction peaks as follows:
Claim 2 adds additional characteristic XRay diffraction peaks. Claims 3 and 4 respectively relate to capsules and tablets comprising the beta polymorph and claim 5 relates to a method of fabricating the tables of claim 4.
The Opposer’s Statement of Case
The Opposer notes that the specification provides support for a material comprising at least 90% of a specific (beta) salt defined by a spectrum of peaks. The main claim, by merely specifying two characterising peaks, effectively claims other polymorphs not necessarily yet discovered and so the claims ‘greedily’ encompass more than the specification teaches.
The justification for the patent is related to enhanced flow properties of the polymorph. However since the claims cover traces of the polymorph, the claimed material as a whole does not show enhanced flow properties.
Based on the introduction to the specification, the Opposer believes that the scope of the patent should be limited to at least 90% of the specific polymorph as characterized by all its peaks. In response to the Applicants claim that the introductory paragraph was included by mistake, the Opposer notes that such a ‘mistake’ is a factual error and to substantiate that it occurred requires factual support, not expert opinion, and so this claim of mistaken inclusion should be struck from the record or given negligible evidentiary weight. To support this argument, Teva notes that Dr Voleman was not the representative of Novartis during the patent prosecution when the paragraph was allegedly mistakenly included.
Furthermore, Teva posits that the average person of the art reading the application would conclude that the invention is for formulations including at least 90% by weight of the (beta) salt of Imatinib Methanesulfonate rendering Dr Voleman’s opinion irrelevant.
Finally, the Opposer claims that there is overlap between the claims of this divisional and of the parent application, and thus the Applicant is trying to obtain two patents for the same invention. However, this line of reasoning was not related to in the summary and seems to have been abandoned.
The Applicant’s Position
The Applicant considers that the specific Example of 90% beta polymorph given in the specification is simply that. It is a non-limiting specific formulation that is provided by way of example.
The Applicant accuses the Opposer of cherry-picking statements from the specification to provide interpretation to the claims, rather than to interpret the claims in light of the specification taken as a complete document. The introductory paragraph was provided for administrative purposes and is not to be used to interpret the patent. Indeed, this paragraph was never intended to be part of the disclosure and was included in the specification by mistake. The parent application claimed the beta polymorph in concentrations exceeding 90% and at the time of filing, the Applicant considered that the practice was to conform the background to the claims, and then to file a divisional with the same specification as the parent, but with different claims. Consequently, the limitations of the introductory paragraph referred to the parent and not the divisional, were inherited from the parent, and are not to be considered as limiting the scope of the claims. Thus according to the Applicant, persons of the art would appreciate that the application in question is a divisional application and the paragraph in question related to the parent patent.
The Applicant claims that the present application claims a new polymorph and is a product claim that is per se patentable. To argue the point they referred to TEVA applications for polymorphs that claim the desired properties of the polymorph, such as flow properties, compaction properties, and the like. These are characteristic of the polymorph but it is the polymorphs itself that is being protected as a new composition of matter.
The properties of the beta polymorph are inherent to the crystalline structure and not to the concentration of the polymorph in the formulation. Since the beta polymorph has inherent advantages, its discovery and manufacture has utility and is thus a patentable invention.
The guidelines for patentable subject matter are given in the Supreme Court rule 345/87 Hughes Aircraft vs. State of Israel p.d. 44(4) 45, 65:
“true the interpretation of patents is not substantially different from the interpretation of any other document, and the standard laws of interpreting papers apply to it. However, due to the special nature and power of patents, additional care must be taken in interpreting since they effectively provide a monopoly in the marketplace. The basic principle is that the patent should be read as a document in its entirety to understand the inventor’s intention as it is expressed in the document…since the patent is primarily directed to professionals in the technological field that the patent considers to be the field of relevance, it should be interpreted using professional knowledge (state of the art) at the time of filing. However, since the patent is supposed to indicate the inventor’s intention, there is some flexibility in giving interpretation to phrases and terms that appear in the claims and the rest of the specification, such as the description, may be used as a dictionary for these phrases and terms. In other words, as a lexicography of the invention.”
Section 13a of the Law states that:
The specification will conclude with one or more claims that define the invention, however these claims must be fairly based on the specification.
Regulation (20)a(3) of the patent regulations 1968 expounds section 13 and requires that the claims are ‘succinct and clear’.
It will be appreciated that the claims define the scope of protection claimed. The claim interpretation should be based on the specification in its entirety – including the description and the figures (Hughes, page 65). However, one cannot import limitations from the specification into the claims:
“The starting point for the appropriate approach is that patent documentation is a one-sided document that the inventor himself writes and he has freedom to write it as he likes. (Catnic Components Ltd.  at 242). A lack of clarity regarding the explanation of a phrase or term in the claims can be made by reference to the specification so long as this is done with reference to the specification as a whole and not selectively in a way to favour the applicant whilst disregarding other phrases in the specification that lead to a different interpretation (Electric & Musical Industries Ld. And Boonton Research Co. Ld. , at 41).”
Section 13(a) deals with the question of whether the claims of the application are fairly based on the specification and whether or not they are sufficiently enabled for persons of the art to practice. The Court of Appeals of the EPO has nicely summed this up as follows:
“Undue breadth is not a reason for refusing a claim under the EPC as long as its subject-matter is novel and inventive, and sufficiently disclosed in and supported by the description.” T 0593/96 INDIGO N.V. (18.11.1996).
See also T 0456/91 Syntex (USA) Inc. v. Debiopharm S.A., (3.11.1993).
In this instance, the Opposer alleges that the claims are not supported by the specification to the extent required by Section 13(a) of the Law since the claims are wider than that supported. The Opposer calls the claims ‘Greedy’. The extent that this term can be used with reference to the requirements of Section 13(a) is given in Appeal 1008/58 Alerican Cyanamid vs. Lepitit et al. page 261 from 4 April 1960. See also Opposition by Teva to IL 142809 to Pharmacia AB from 26 February 2015.
In his Opinion from 1 December 2013, Dr. Mark Zakrzewski (Teva’s expert witness) notes that the invention clearly specifies a 90% concentration of the beta phase.
“34. The alleged invention is explicitly described in the Patent Application as a methansulfonate salt of Imatinib Mesylate comprising “at least 90% by weight of crystals of the β-modification…” or “in essentially pure form”.
Based on this, the Opposer considers that claim 1 which lacks this limitation is wider than that supportable under Section 13(a).
Consideration of the Application itself shows that there is no certain preference to limit the concentration of the beta phase. For example, page 3 states:
“The invention relates to an acid addition salt of a compound of formula I comprising non-needle-shaped crystals, especially the β-crystal form of the methanesulfonic acid addition salt of the compound of formula I.
The invention relates especially to a particular, form of the monomethanesulfonic acid addition salt of a compound of formula I,
comprising at least 90% by weight of crystals of the β-modification, said crystals of the β-modification showing on X-ray diffraction a peak at an angle of refraction 2theta of 20°, said peak having a relative line intensity of 65 as compared to the most intense line in the diagram”.
Further on, on page 4 of the specification, the following is stated:
“The term “essentially pure” is understood in the context of the present invention to mean especially that at least 90, preferably at least 95, and most preferably at least 99 per cent by weight of the crystals of an acid addition salt of formula I are present in the crystal form according to the invention, especially the β-crystal form.
The invention expressly relates also to those forms of the methanesulfonic acid addition salt of a compound of formula I in which crystals of the crystal form according to the invention, especially the β-crystal form, are present in essentially pure form…”.
From the above it is clear that the specification does relate to the beta phase in a manner that does not necessitate limiting it to a preferred concentration. Apart from the opening paragraph which will be discussed separately, the specification uses terms such as ‘particularly’ and ‘especially’ with regards to concentrations and does not limit to these desirada.
The reader will appreciate that the patent relates to the non-needle-like beta phase but not to specific concentration ranges. See Section 22 of Dr Bates’ opinion on behalf of the Applicant:
“22. Contrary to Dr. Zakrzewski’s assertions, the specification teaches and enables form β per se, without any purity limitations. An “essentially pure” form β is one of the preferred embodiments of the invention, but by no means reflects the entire scope of the invention. Dr. Zakrzewski apparently selects a couple of paragraphs which highlight a preferred embodiment, disregards the teaching of the specification as a whole will readily understand that the invention is the discovery and development of the novel form β and that the invention is not limited to form β only when it is “essentially pure”.”
As to the practice of claiming new polymorphs, Dr Bates opines:
“Indeed, just like new chemical entities, novel polymorphs are claimed per se without quantitative purity limitations. At the most, quantitative limitations are a preferred embodiment, as in the instant case. For the sake of demonstration, I instructed applicant’s counsel to search polymorph patents issued to Teva by the USPTO. Overall, 78 patents claiming polymorph forms were found. 77 patents out of 78 patents claim the polymorph forms per se, without “quantitative” or “purity” limitations…”
The Applicant explained that the introductory paragraph was the result of the Examiner requiring the specification of the parent to be conformed to the claimed invention, and then was inherited in the divisional application. This claim, related to in Dr Voleman’s opinion, relates to factual matters. Commissioner Kling concurs with the Opposer that Dr Voleman is not the ‘correct’ witness to testify that this was a mistake and does not have first-hand knowledge regarding that which she is about. Such a claim requires support by an affidavit and is a matter for first-hand testimony and not for an expert witness to hypothesize about.
That said, the state of affairs is not sufficient to warrant deviating from the general principle stated in the Hughes Aircraft Decision, that the specification should be considered ain its entirety. From this perspective, the Commissioner is willing to accept the Applicant’s claim that the introduction is not indicative of the scope of the invention and cannot be relied upon to the exclusion of the rest of the specification to explain that scope of the application. A person of the art who reads the document as a whole would not rely on the introductory paragraph alone, but would read the patent application in its entirety.
The Opposer alleges that the claimed invention does not have utility since it does not demonstrate the advantages of the beta polymorph when present in minor proportions.
It is true that amongst other requirements, in accordance with Section 3 of the Law, a patentable invention has to have utility. The utility is a requirement that the patent application as a whole must satisfy as stated by Judge Hendel in Appeal 5041/13 Anat Gabai et al vs. Aminach Mattresses, 21 January 2014:
Reading the main paragraph that gives the requirements for patentability teaches that “utility” is the second criterion of the four criteria for patentability. This is not by chance. All patent applications are expected to have utility.
The nature of the utility requirement is discussed by Judge Netanyahu in Appeal 665/84 Sanofi vs. Unipharm p.d. 41(4) 729:
At the time of filing the Application, it has to include a promise of utility. If this is the case, generally the requirements of Section 3 are met. Proof of this promise will be required at the Opposition stage, if this is submitted as grounds for Opposition, or in a cancellation proceedings or infringement action. In Oppositions, the burden of proof is on the Applicant since the patent has not yet issued; in cancellation or infringement proceedings the burden is on the challenger / infringer.
See also the Opposition to 179840 Aminach Furniture Industries Ltd vs. Anat and Moshe Gabai, 20 November 2012.
In this instance, it appears that the promise that is the basis of the Application is the advantage of the Beta phase regardless of concentration. (There is no dispute that the beta phase is novel and inventive). The advantages that Novartis’ witness Dr Bates has alleged are the improved flowability and compactability of the beta phase when compared with the alpha phase, and the parties concur that these properties are desirable in pharmaceutical formulations.
To the extent that the claimed properties are substantiated, they are substantiated for formulations with a greater than 90% concentration of the beta phase. The Applicant did not demonstrate or provide evidence of these properties in lower concentrations.
As stressed above, in the Sanofi ruling, the court emphasized that the claimed advantages have to be proven at the opposition stage if the utility is challenged. Some evidence is required to show that the promise is attained, although not necessarily the quantity of experimental evidence that would be required were the opposers to actively provide counter-evidence.
In this instance, the Applicant continues to allege that they deserve a patent for formulations with even minimal beta content. The Opposers have noted that there is no evidence that such low concentration formulations have advantages over the alpha phase and the Applicant has not provided evidence to support their claims or a reasonably convincing counter-argument in response to the Opposer’s reasoning. This is not to say that had the Applicant’s expert witness related to this, his arguments would have been found convincing – See Opposition ruling concerning IL 143977 Unipharm vs. AstraZenica AB paragraph 44.
In this instance, at the joint request of the parties, no witness is being cross-examined. From this it is clear that the Applicant has not substantiated their claim that formulations with low concentrations of the beta phase have sufficient utility to be patentable.
The overlap between the claims of the Divisional Application and those of the Parent
In addition to the above, the present application is not patentable due to the significant overlap between the claims and those of the parent patent.
Whilst it is true that in their summation, the Opposer abandoned this line of reasoning, the Commissioner does not consider that this fact alone is sufficient for the matter to be dropped since oppositions are a continuation of the examination process and the patentability question is once again opened. The purpose of oppositions is to ensure the purity of the register and is a continuation of the administrative process (See Opposition to 136482 Bromium Compositions vs. Albermarle Corporation USA, 7 November 2010.
Section 2 prohibits granting a patent for an already patented invention. See also the IL 203972 Novartis decision. To address the issue of double patenting it is necessary to consider the scope of the invention. The scope of the invention may be learned from the total breadth of protection that the patentee receives (see 2626/11 Hassin Fire Industries vs. Koniel Antonio (Israel) Ltd. 14 November 2013 paragraphs 35-38.)
Independent Claim 1 of the parent application claims the beta phase of the Imatinib Methanesulfonate salt at concentrations of at least 90% with a strong 2theta XRay defraction peak at 20° as follows:
Thus the parent claims the same beta Imatinib Methanesulfonate salt concentrations of at least 90% whereas claim 1 of child patent does not include a minimum concentration. The specifications are the same apart from minor differences that are insignificant, and so the claim construction considerations used to define the terms are the same in both the parent patent and in the divisional application. Despite different phraseology the scope of the claims overlap.
The differences are in the non-needle like form of the crystal, the characteristic XRay diffraction peaks and the concentration limitation of the parent. Careful examination indicates that the same polymorph is covered by both cases, although defined differently, with the sole difference being the concentration limitation in the parent is not in the divisional application and this removal of the concentration limitation is the feature that the Applicant points to as being the patentable feature. However no advantage is given for the low concentrations covered by the divisional application. The Applicant claims that the parent patent and divisional application cover different aspects of the invention. However, the concentration is not an aspect warranting separate registration.
The IL 174082 Application is refused. Costs are applicable as per Commissioner Circular M.N. 80.
It seems to me that the person of the art considering a patent publication to understand the scope of the claims is a patent attorney with pharmacological background, or a team including technical people and patent counsel. I don’t believe that any industrialist (except possibly Dr Zebulun Tomer of Unipharm who has been challenging blockbuster patents for years and has been known to file oppositions by himself) would construe the claims of a pharmaceutical patent without seeking legal advice so Dr Volman can be considered as an expert.
The Commissioner is correct that there is no obvious or demonstrated utility for the lower concentrations.