Biopharmaceuticals or Biologics represent some of the best accomplishments of modern science. Particularly, biopharmaceuticals refer to pharmaceutical substances or drugs derived from biological sources. These drugs are increasingly being used in nearly all branches of medicine and have become one of the most effective clinical treatment modalities for a broad range of diseases, including cancers and metabolic disorders. They are produced using biotechnology techniques especially genetic engineering, hybridoma technology, recombinant human technology, gene transfer, or antibody production methods. Biopharmaceuticals are known to target only specific molecules, rarely causing the side effects associated with conventional small‐molecule drugs.
Additionally, compared with conventional drugs, they are known to exhibit high specificity and activity. The first biopharmaceutical substance approved for therapeutic use was biosynthetic human insulin made via recombinant DNA technology in 1982 under the trade name Humulin. The insulin was developed by Genentech but licensed to Eli Lilly and Company, who manufactured and marketed it starting in 1982. In India, most of the growth in Indian biopharmaceuticals is because of vaccines, compared to therapeutics and diagnostics. Indian companies manufacture an increasingly wide range of biopharmaceutical products such as recombinant insulin, erythropoietin (EPO), G-CSF, recombinant hepatitis-B vaccine, streptokinase, interferon alpha-2b, rituximab, and an anti-EGFR mAb product.
Patenting Biopharmaceuticals
Biopharmaceutical patents play a major role in promoting innovation and research. The global advancements in genomics, the pharmaceutical industry, biotechnology, and personalised medicine have driven the research and development in biopharmaceuticals. Biopharmaceutical patents not only provide exclusive rights but simultaneously impact drug availability and affordability. Within India, the landscape of biopharmaceutical patents has undergone notable transformations, shaped by a combination of regulatory adjustments, judicial interpretations, and international accords.
Multinational companies are actively pursuing patent protection for their biopharmaceutical innovations and are utilising intellectual property rights to safeguard investments, secure market exclusivity, and gain a competitive edge. One such case relates to a breast cancer drug, Trastuzumab, which was manufactured by Roche and Genentech Inc. and was sold under the brand names of Herceptin, Herclon, or Biceltis for the treatment of human epidermal growth factor receptor 2-positive (HER2+) breast cancer. A representative list of a few other granted cases is given below.
| Patent Number | Subject Matter |
| IN 525043 | Vaccine Adjuvants |
| IN 501198 | A Human Insulin Derivative for Real-time Monitoring of Insulin Quality and Process for Synthesizing Thereof |
| IN 447336 | Vaccine Against Riemerellosis |
| IN 433684 | A Shigella Nanovaccine and Process for Synthesis Thereof |
| IN 506544 | Monoclonal Antibodies Specifically for Phosphoprotein of The Human Respiratory Syncytial Virus And The Methods of Use |
| IN 445422 | Rastuzumab Conjugated Drug-Loaded Pegylated pH-Sensitive Nanocarriers Composition for Breast Cancer Treatment and Its Synthesizing Process |
| IN 398168 | Novel Humanized Anti-Cd-19 Chimeric Antigen Receptor, Its Nucleic Acid Sequence and Its Preparation |
Challenges and Judicial Interpretations
Despite promising growth prospects, one of the key challenges in biopharmaceutical patenting is meeting the patentability criteria, i.e., satisfying the three-prong requirement of novelty, inventive step, and industrial capability specified under Section 2(1)(j) of the Indian Patents Act. Besides this requirement, the invention must not fall within the realm of non-patentable inventions listed under Section 3 of the Patents Act 1970. Biopharmaceutical-based inventions are specifically scrutinised under Section 3(b), Section 3(c), Section 3(d), Section 3(e), and Section 3(j) of the Indian Patents Act, 1970 and imposes stringent requirements for patenting the incremental innovations and pharmaceutical derivatives.
Section 3(b) restricts patenting of an invention if its use or commercial exploitation is “contrary to public order or morality” or “causes serious prejudice to human, animal or plant life or health or to the environment”. For example, only genetically modified biological materials that cause no prejudice to human, animal, or plant life or the environment are patentable.
Biopharmaceutical inventions involving or claiming living organisms and naturally occurring substances are also often prohibited by the provision of Section 3(c) of the Act. Although Section 3(c) of the Act does not debar the patenting of biopharmaceuticals per se, the provision often impacts certain aspects of biotechnological inventions, such as genetically modified organisms (GMOs), cell lines, or naturally derived biomolecules. Even the Guidelines for Examination of Biotechnology Applications for Patent clarify that the scope of this provision is restricted only to those proteins that are ‘directly isolated from nature’.
Therefore, it is imperative to demonstrate that products or compositions claimed in the patent application are novel per se and do not merely claim a naturally occurring substance or a living organism. In Genmab A/S vs Assistant Controller of Patent and Designs, the Hon’ble Court held that “non-living substances occurring in nature or isolated from nature are not eligible for patents. However, a synthetic version of a substance that rarely occurs in nature and is required to be produced in large quantities for the treatment of serious illnesses is not excluded from patent eligibility if other criteria such as novelty or technical advancement are satisfied”.
Further, Section 3(d) of the Indian Patents Act aims at preventing evergreening and promoting access to affordable medicines. “Evergreening” refers to a strategy by which an additional “secondary patent” is applied by minor formulation or other changes of the parent patented molecule, of which the patent period is going to expire. Therefore, the provision of Section 3(d) has significant implications for the patentability of pharmaceutical and biopharmaceutical inventions, requiring patent applicants to demonstrate an enhanced therapeutic efficacy over existing treatments. Further, the efficacy data may include experimental data demonstrating claimed enhancement by comparative studies or clinical trial data, etc.
Another challenge lies in meeting the patentability criteria laid down in Section 3(e) of the Act. Particularly, in patent applications wherein a combination of drugs or pharmaceutical compositions is being claimed, the inventor/applicant is required to establish the synergistic effect. Although the term “synergism” is not defined in the Act, it is commonly referred to as the interaction of two or more things that produce a combined effect greater than the sum of their separate or individual effects.
Moreover, the Guidelines issued by the Patent Office provide clarity in this respect; specifically, the Guidelines for Examination of Patent Applications for Pharmaceuticals-based inventions issued by the Indian Patent Office states that “Claims related to compositions obtained by mere admixture resulting in aggregation of the properties of the individual components are not patentable under Section 3(e) of Act. However, in composition, if the functional interaction between the features achieves a combined technical effect which is 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”.
The Guidelines for Examination of Biotechnology Applications for Patent states, “when old integers placed together have some working interrelation producing a new or improved result, then there is patentable subject matter in the idea of the working interrelations brought about by the collocation of integers“.
Thus, said guidelines clarify that the patent applications claiming the compositions or combination of drugs may be patentable provided that such effect is non-obvious and results in synergism. Also, the combined technical effect can be based on one or more aspects such as improved efficacy, reduction in the frequency of doses, improved stability or shelf life, optimisation of pharmacokinetics or bioavailability of the active ingredients, reduction of side effects, reduced toxicity, the possibility of administration of the drug by a different route or improvement of the patient’s compliance with the treatment, etc. In Stempeutics Research v Controller [OA/03/2017/PT/CHN], the IPAB held that the applicability of Section 3(e) is valid wherein a claimed product is obtained by combining known or already existing ingredients, and the burden of showcasing synergistic effect for such product is therefore necessary.
Furthermore, one of the biggest barriers to the patentability of biopharmaceuticals is Section 3(j) of the Indian Patents Act, which excludes from patentability “plants and animals in whole or any part thereof”, “seeds, varieties and species” and “essential biological processes for production or propagation of plants and animals”. In this respect, in 2002, a path-breaking Dimminaco case (Dimminaco v Controller of Patents and Designs & Others) came before the Calcutta High Court, related to a process for the preparation of a live attenuated vaccine for protecting poultry against bursitis infection.
Although it was stated that the claimed process was only a natural process devoid of any manufacturing activity and the end product contained live attenuated material, it was clarified by the Hon’ble Court that “if the end product is a commercial and vendible entity, and for that, presence of living virus /microorganism in the end product is necessary, it cannot be a bar to its patentability”. Similarly, it was also clarified in an appeal filed by Monsanto before IPAB against the Controller’s decision wherein after considering the matter, the IPAB significantly overruled the findings on Section 3(j) of the Indian Patents Act, 1970 and affirmed that the method claimed by Monsanto included an act of human intervention on a plant cell and produced some changes in the plant cell, which took it outside the proscription of Section 3(j).
Conclusion
Biopharmaceutical products generally take a long time to get from inception to commercialisation with rigorous research efforts. With the augmentation of emerging technologies, there is indeed a reduction in the time required to bring a biopharmaceutical product to market and also to minimise the process of designing molecules. Although biopharmaceutical companies also appear to be changing, innovation continues to thrive in India, driven by advancements in scientific research and collaborative projects between academia, industry, and government agencies despite the challenges. Further, patent litigation and enforcement are playing a pivotal role in shaping the landscape of biopharmaceutical patents in India. However, the patent applicants or stakeholders must steer regulatory complexities, address patentability challenges, and foster collaborative ecosystems to sustain momentum and drive meaningful impact in healthcare innovation and affordable access.
