The patentability of compositions is governed by two key provisions in the Indian Patents Act, 1970 (“the Act”), i.e., the requirement that in order to be patentable, an invention must be novel, include an inventive step, and have some industrial applicability (Section 2(1)(j)), and the requirement that a substance obtained by a mere admixture resulting only in the aggregation of the properties of its components or a process for producing such substance is not patentable (Section 3(e)). When read together, it follows that in order to be patentable, a composition must exhibit non-obvious or unexpected synergism.
This note discusses synergism and the patentability of compositions in India, in two parts, the first describing the ways in which synergistic effect may be demonstrated, and the second detailing the manner in which patent applications for compositions have been prosecuted by the Indian Patent Office (“IPO”) over the years. The second part can be read here.
What is Synergism?
The term “synergism” is not defined in the Act, but in common usage, refers to the interaction of two or more things which produce a combined effect greater than the sum of their separate effects.
According to the Guidelines for Examination of Patent Applications in the Field of Pharmaceuticals issued by the IPO, in a composition, if the functional interaction between the features achieves a combined technical effect greater than the sum of the technical effects of the individual features, it indicates that such a composition is more than a mere aggregation of the features.
Depending on the end objective, a composition having more than an additive effect, an enhancement effect, or unexpected behavior may be regarded as exhibiting “synergism” under the Act. These compositions may be patentable provided that such effect is non-obvious or unexpected.
Examples of synergistic effects include improved efficacy, improved stability or shelf life, improved dissolution profile, or reduced toxicity. Some specific examples are discussed below:
- More than the additive effect: E.g., a combination of multiple drugs that exhibit improved efficacy, lower toxicity, less adverse side effects, due to the requirement of lower doses of the drugs. For instance, the effect of a combination of acetaminophen, aspirin, and caffeine is considered significantly more than the additive effect of any of the drugs, taken singly or in a combination of two drugs.
In Indian Patent Application (“IPA”) No. 201818015075, the Controller held that the claimed herbicidal composition comprising known herbicides Fluroxypyr and Metamifop exhibited synergistic effect.
- Enhanced effect of the active component. E., an insecticidal composition containing an active and non-active component, where the non-active component greatly enhances the activity of the active component. For instance, the addition of sesame oil to pyrethrin markedly increases the efficacy of pyrethrin (US2202145A). Similarly, a polyacrylamide supersorbent material is found to enhance the potency of pesticides (US5037654A).
- Reduced side effects/disadvantages: g., when the combination of an active component with active or non-active components reduces side effects or toxicity. For instance, when albumin is combined in an effective amount with paclitaxel in an injectable composition, it is said to reduce some side effects of the pharmaceutical composition (US8138229B2).
In a pre-grant representation against IPA number 3140/KOLNP/2007, the Controller held that “in presence of lactose the epimerization of tigecycline is less and therefore tigecycline becomes more stable. Therefore … the formulation of the instant invention is not a mere admixture but shown synergism /surprising result and therefore cannot be held non-patentable under section 3(e) of the Act”.
- Modification of form or function: E.g., when two or more components of a composition interact to change or modify each other’s form or function. For instance, in IPA No. 8933/DELNP/2015, the Controller allowed the claim for a composition comprising a metal complexing agent and a corrosion inhibitor comprising a metal ion (chromium). Here, the applicant demonstrated how the different components interact to convert the surface chemistry of the metal substrate.
- Formulations designed for a specific route of administration: E.g., what happens when the invention lies in the finding that one type of formulation (say, an oral formulation) is better than another (say, an injectable formulation)? If the finding is unexpected or surprising, in that perhaps it is in contradiction with preliminary research, or the prior art teaches away from the invention, the claimed composition may meet the requirement of inventive step. However, the requirements of Section 3(e) and inventive step are treated as mutually exclusive under the Act. In such cases, an enquiry must be made regarding the reason for the better performance; if the reason is interaction or synergism between the various components, then the composition may be patentable.
In IPA No. 10885/DELNP/2015, the Controller concluded that the improved effect of the composition was because of the dose and how it was administered, rather than due to the interaction of the constituents of the composition, and thus, the relevant claims were not patentable under Section 3(e). In this application, the data provided in the specification merely established the fact that the active compound in claimed composition when given orally showed better pharmaceutical activity over intraperitoneally administration of claimed pharmaceutical composition, but it failed to show any synergistic effect of the constituents of the composition.
Synergism and Ratios
Synergism sometimes depends on the ratio or concentrations of the components present. In IPA No. 10885/DELNP/2015, the Controller concluded that the pharmacological effect or activity of the compound observed was because of the dose and how it was administered, rather than due to the constituents of the composition, and thus, the relevant claims are not patentable under Section 3(e).
Similarly, in IPA No. 201711028226, a claim for a repellent composition was allowed because the specification provided evidence for the surprising and unexpected effect of a 3:2 combination of the components of the composition.
Composition based on novel components
Section 3(e) comes into effect only when a composition contains known components.
The Guidelines for Examination of Biotechnology Applications for Patents issued by the IPO, which states that “when old integers placed together has some working interrelation producing a new or improved result, then there is patentable subject matter in the idea of the working inter relations brought about by the collocation of integers” [emphasis added].
The Intellectual Property Appellate Board (IPAB) in OA/16/2016/PT/KOL clarified this position. In this case, the composition, among other ingredients, contained a novel component, ‘pooled MSCs’. The IPAB held that the applicant did not need to show synergism for the said composition.
Often, applications directed to novel compounds/polypeptides also include one more claim directed to a composition comprising said compounds/polypeptides with some excipients. In such cases, the examination reports usually include an objection under Section 3(e). The IPO was inconsistent in handling these matters, with some Controllers allowing such applications while others refuse the grant; but IPAB’s clarification in OA/16/2016/PT/KOL has brought much-needed clarity on this.
It is useful to recall that Section 3(e) deems mere admixtures not patentable. From the preceding discussion, it emerges that under Section 3(e), a mixture would be called a mere admixture only when “known” substances are combined AND such combination merely results in an “additive effect” of the said substances i.e., the total effect of the composition is equivalent to the sum total of the individual components.
To address an objection under Section 3(e), the applicant could rely on existing specification data or substantiate it with additional data by way of an affidavit from the inventor or a person having reasonable experience in the art. In order for the application to succeed, this additional information must demonstrate that the combination of the claimed ingredients results in a technical effect greater than aggregation of properties of individual elements.
Ideally, prosecuting a patent application in India that includes claims for a composition would require demonstrating that the composition exhibits some kind of unique and unexpected synergism that has not been encountered in the art previously. As discussed in this note, synergistic effects can be shown in many ways, which would certainly improve the likelihood of grant.