We normally come across many types of patent claims. A patent kit type claims refers to a claim where the inventor wants to patent the selling of two or more products together in a 'kit' to be combined at the time of use only. Such kits normally come with instruction for use by the end user. These types of claims are useful in any type of business but they are found commonly in biotech, paint and coating industry products. More particularly, in combination therapy cases the invention lies in the finding the enhanced therapeutic benefit of using the combination in a particular manner. In such cases the therapeutic benefits is derived from the synergistic or inter working relationship between the active ingredients in the body. In Indian context common hurdle for patenting combination therapy is Section 3(e), which specifically bars patentability of "a substance obtained by mere admixture" and any process for its preparation. Combination vaccines therapy invariably invite objection from IPO under this clause. However, the existing IPO practice allows a composition therapy claims comprising of known therapeutic components provided that it exhibits synergism. What amounts to synergy in a combination therapy claims lacks a clear statutory definition leaving IPO controllers with lot of discretion to decide patentability issues on a case to case basis.
Combination drugs are moving fast in the acceptance of particular therapy in the modern medicine. It is likely to move further and further in the direction of combined therapies where special products with flexible methods of administering would be required. If the combination of the two components has been justly acknowledged as inventive in the specification there should no bar to provide the patent protection to such combinations. So long as such a preparation is envisaged as a narrow physical combination of the components or simply a union of mixture just to differentiate the claimed product from a state of the art which may include the a medical kit, collection or package containing the two agents in separate but adjacent form for their known independent applications in medicine, it could be afforded patent protect. This principle has been followed in various patent jurisdictions to climb the hurdle of novelty. Another hurdle that such claims must cross is the requirement of representing a functional unity in the combination.
Kit of Parts claims
Kit-of-parts claims basically relate to a combination product which provides the two actives ingredients together in a package ready for co-administration. As a kit-of-parts of claim it is not essential to establish a true combination in view of the physical separation of the individual components. The mere loose association of known components does not in itself turn them into a functional unity. In a kit type of claims where combination of component is envisaged, a direct interaction between the components is a precondition for the purposive use (cf. e.g. lock and key, match and striking surface, two-component adhesive). Even if components in the claimed combination do not enter into such a direct interaction with each other, the indication of purpose for the combined therapy may re-establish the unity of the product as a functional amalgamation of its two components, if it represents a genuine restriction to the specified application.
Compositions and admixtures : kit type claims
Section 3(e) of the Patents Act 1970 as amended put a bar on patenting the substance obtained by a mere admixture resulting only in the aggregation of the properties of the components thereof or a process for producing such substance. When we talk about composition in pharmaceutical terms such a composition is characterized as a product (substance). Since composition is not defined in the act we may take its dictionary meaning. According to the Oxford English Dictionary composition refers to "A condition consisting in a combination or union of several things; a combination, aggregate or mixture". According to Le Robert, Dictionnaire Alphabétique et Analogique de la Langue Française "composition" may also have the meaning of "combinaison" - especially in chemistry - or in general terms "assemblage". The combined products intended under section 3(e) for therapeutic, surgical or diagnostic methods also include compositions in which the components are presented side by side and can therefore be applied simultaneously, separately or at intervals to one and the same human or animal body. Since the components referred in section 3(e) cannot attain the advantageous effect according to the invention independently of each other, the joint effect justifies the unity of the combined product. If the applicant is able to justify and substantiate the better or synergistic effect as a result of the limitation by the indication of purpose of the area of protection of the claim under the conditions he would be in a position to remain outside the provision of section 3(e). Even in cases where the components are presented side-by-side and not as a union, subject-matter of kit type claim would fulfill these conditions. Section 3(e) refers to the cases in which substances or compositions already belong to the state of the art. This kind of 'kit type claims' permits particular types of known products to be claimed. However, the IPO is not consistent in taking the view that such claims in accordance with section 3(e) cannot be denied to the applicant even if the product as such is new to some extent when compared with mere admixtures. One must understand that this category of claims can serve as a fall-back position and protects, for example, against the consequences of incidental previous publications of the product even in any other field.
Position in US: Cytostatic therapy case
In this typical kit claim case the applicant claimed kits useful for cytostatic therapy where a combination of oxazaphosporin with sodium salt of 2- mercaptoethane sulphonic acid for simultaneous or sequential use is recommended for relieving pain associated with injecting oxazaphosporin cytostatic agent. It is known that cyclohexylamine salt or a lysine salt cytostatic when injected in a vein gives a severe long-lasting pain. Apparently this pain is due to a specific reaction of the cystostaic agent with sensitive nerve-ending or pain receptors. In US4770870A it was disclosed that "The pain is not the result of a inflammatory tissue reaction. It occurs even with no histologically detectable tissue damage. Surprisingly this pain is prevented by the use, e.g. simultaneously of the compound of formula II, for example 2-mercapto-ethanesulfonic acid in the form of sodium salt or N-acetyl cysteine." Based on this disclosure the patent was granted to such cytostatic therapy.
Reasons for Rejection of Combination claims in EPO [Cytostatic therapy]
When similar application was filed in EPO [Patent application number 78 101 583.9, it was refused by decision of the Examining Division of the European Patent Office. The patentability of the subject-matter of claims 6 to 10 was acknowledged in the decision, but claims 1 to 5 directed to uses of substances in cytostatic therapy were considered not patentable. Claims 1 was worded as follows:
This combination therapy claim was initially rejected by EPO examiner on the ground that each component of the preparation was known and their respective pharmaceutical effects were also known. The applicant filed appeal in the EPO board.
Grounds for the appeal [Cytostatic therapy]
- The applicant submitted that this invention is of great importance for chemotherapy with oxazaphosphorin cytostatic agents, used frequently in the treatment of cancer. Treatment of patients with such cytostatic agents leads to severe damage to the kidney, urinary passages and bladder, so that as a rule the therapy has to be interrupted or completely terminated.
- The Applicant contended that the impugned invention is based on the finding that this damage does not occur when sodium 2-mercapto-ethane-sulphonate is also administered. The detoxicating function of this salt on the oxazaphosphoring metabolites can be observed, for example, when both components, are administrated simultaneously, but it is also beneficial to use these components separately or at intervals.
- The claimed product may therefore also contain the kit of the two active ingredients in ampoules for the intravenous injection. In view of this comprehensive, new and indisputably inventive teaching, adequate protection must be claimed for all these variants, at least in the form of product protection."
Reasons for allowing combination claims by EPO Board of appeal
The appeal was heard by the Board of appeal EPO and the Board allowed such combination. The Board observed that although first-mentioned component of the product was known, and the second component was also a known as mucolytic agent but as per the documentary prior art available to the board, the two active ingredients had never been used together for a new joint effect and were unknown as a composition. The active ingredients according to the Board observation are administered preferably at the same time (cf. page 5, lines 14 and 15 of the application) according to the invention do not therefore represent a mere aggregate of known agents, but a new combination with the surprising, valuable property that the severe side-effects to be expected when administering the cytostatic agents are absent as a result of the detoxicating effect of the sodium 2-mercapto-ethane-sulphonate.
The Board further observed that such a preparation would have to be envisaged as a narrow physical combination of the components, i.e. a union of mixture, to differentiate the product from a state of the art which includes the possibility of a medical kit, collection or package containing the two agents in separate but adjacent form for their known independent applications in medicine.
The Board also made it clear that the active ingredients which were administered preferably at the same time according to the invention did not therefore, represent a mere aggregate of known agents, but a new combination with the surprising, valuable property that the severe side-effects to be expected when administering the cytostatic agents were absent as a result of the detoxifying effect of the sodium 2-mercapto-ethane-sulphonate.
Synergism in Indian Context
In the cases where composition of known substances is claimed as a combination kit, the applicant is expected to substantiate it with existence of synergistic results or unexpected /surprising results. Indian patent office practice varies from Controller to Controller. For example the patent 256057 was granted for administering to a patient Calcitonin (anti osteoporosis) followed by Glucocorticoid (anti-inflammatory) for a "Pharmaceutical composition comprising a calcitonin and a pharmaceutically acceptable carrier". This patent was allowed after the applicant amended the claims to a synergistic composition of Calicitonin and Glucorticoid where the two components come into contact with each other only in human body. Even the method claim for preparing the composition by bringing the two compounds into contact with each other at a locus was allowed. But in similar case where composition of combination claim such as " A composition for use in long-term treatment of fibromyalgia and its symptoms in a patient suffering from fibromyalgia comprising milnacipran, or a pharmaceutically acceptable salt thereof, and a second active compound administered adjunctively with the milnacipran " was denied for the reason that applicant failed disclose or substantiate through examples the synergistic effect claimed in the reply arguments.[ Cypress Bioscience, Inc. application 3183/DELNP/2008]. It was refused under section 3(e). It seems that one of the principal reasons for refusal of second case was the non-disclosure of the synergistic effect in the specification. However, it does give a hope to patent a new uses for existing medicines provided that they are claimed as synergistic combinations supported by the disclosure of data in the specification.
Need for indication of purpose in a claim
Most of the kit type claims give the preamble as to the purpose of the invention. The applicant is not duty bound to indicate purpose in the claims but such an indication of purpose in claims is technically meaningful if the skilled person is thereby made aware of further, not expressly specified or yet to be specified characteristics of the product, or of additional conditions for a process, which are necessary for the intended use or operability (e.g. a particular selection, quality or inter-relation of the various components). In other words the indication of purpose with physical relevance of the invention to the indication of purpose would provide meaningfulness and clarity to the claim. By contrast, indications for therapeutic use under section 3(e) are necessarily significant and may under certain conditions even provide grounds for the novelty of a known product, without requiring any additional identifiable or verifiable physical characteristics. But cautiously such conditions should restrict the subject-matter appropriately, so that already known applications of the subject-matter are excluded from the claim.
Protection for the combined product as a collection of essential components with a corresponding indication and with reference to joint use, moreover, in the therapeutic field also exceptionally justified by the fact that certain active substances do not necessarily bring about their joint effect at the same time or directly. For example when a combination is taken orally, one component may be absorbed in the stomach, whereas another merely passes into the intestine. The kit-of-parts of the essential components of the combination does not therefore need to appear in molecular or microscopic dimensions according to the inventive teaching. It would not be justified if such advantageous therapeutic combinations for solving the longstanding problem were not included in the patent protection. Modern medicine may move further and further in the direction of combined therapies which require special products with flexible methods of administering. Be aware that the individual components of the combined product in the kit type claims are themselves known for some therapeutic applications. Therefore, these claims, by expressly including the separate presentation of those components, are indeed to be regarded as limited to the joint use of the combined products, so that the individual applications according to the state of the art are excluded. The indication of purpose provided for in section 3 (e) for such products serves this objective, so long as its formulation complies with the other requirements of section such as synergistic effect/ surprising results.
The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.