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5. For purposes of inter alia improving stability during freeze- drying, storage, transportation and administration, excipients are added to the API. An excipient used to protect the API during the freezing phase is called a cryoprotectant and an excipient used for the same purpose during the drying phase is called a lyoprotectant. On the basis of functions, excipients used in biologics may be categorised inter alia as stabilizers, lyo/cryoprotectants, buffering agents, bulking agents, surfactants, tonicity agents, pH adjusting agents, solubilizing agents, anti-microbial preservative and anti-adhesive __________ Page 6 https://www.mhc.tn.gov.in/judis ( Uploaded on: 26/08/2025 07:59:11 pm ) agents. It should also be borne in mind that an excipient could perform more than one function in a formulation. Typically, excipients form the bulk of the formulation in comparison to the API.

“.... The compositions may be prepared in liquid form, or may be in dried powder, such as lyophilized form.” Although the use of excipients is also referred to in column 19 of D4 and ingredients like sucrose are referred to, the process of lyophilizing the therapeutic peptibody is not recited therein. D5 discloses a lyophilized composition of IL-12 by use of excipients, but it does not describe the method of lyophilizing the therapeutic peptibody of Formula V. In fact, D5 contains only composition claims and no method claims. I also find that independent claim 9 recites the use of specific excipients of specific excipient categories, such as buffering agent (at a specific pH), bulking agent, stabilizing agent and __________ Page 31 https://www.mhc.tn.gov.in/judis ( Uploaded on: 26/08/2025 07:59:11 pm ) surfactant, at specific concentrations. Therefore, the process described in independent claim 9 cannot be characterized as the mere use of a known process. Consequently, the rejection under Section 3(d) of the Patents Act is not sustainable. I turn next to the rejection under Section 3(e) of the Patents Act.
Method of lyophilization, reconstitution and kit was disclosed in D1, D3, D5 and D6. It would be obvious to person skilled in the art to lyophilize a known peptibody which was disclosed in the prior art for the improved shelf life. The excipients and the range of excipients are already disclosed in the prior art documents. The desired effect claimed by the applicant can be obtained by __________ Page 40 https://www.mhc.tn.gov.in/judis ( Uploaded on: 26/08/2025 07:59:11 pm ) optimization, which cannot be considered as a technical feature for inventiveness as it would have been obvious to one ordinary skilled in the art. There is no data regarding pre-lyophilization and reconstituted formulation to compare the improved technical effect/storage stability. The applicant has provided data for optimization of various excipients and concentrations. The technical advance as compared to the existing knowledge was not established in the specification. Other than an optimization, no technical advancement has been clearly stated in the specification. Hence inventive cannot be acknowledged for the instant invention and objection u/s 25(1)(e) stands valid.” Prior arts Six prior arts were cited in the FER. Out of these, the sixth prior art was non-patent literature. In the first hearing notice dated 27 April 2016, D3 and an additional prior art labelled as D7, WO 2000024782, were cited. By reply dated 24 June 2016, the appellant contended that D7 is directed at the fusion of the Fc domain of a __________ Page 41 https://www.mhc.tn.gov.in/judis ( Uploaded on: 26/08/2025 07:59:11 pm ) peptide to increase the in vivo half life and that it does not teach the use of specific excipients. Later, in the pre-grant opposition, the second respondent cited five prior arts, which were labelled therein as prior arts D1-D5. Only these five prior arts were placed on record in this appeal. Hence, in order to decide whether this ground of rejection is sustainable, a discussion of these cited prior arts is warranted. This exercise should be carried out by donning the mantle of a PSITA. The relevant art in this case is the formulation of biologics, and PSITA would be a formulation scientist. While knowledge and skill would be attributed to the notional PSITA, excellent/outstanding skill and ingenuity would not be attributed (see Rhodia Operations).
“Because every protein is different and reacts differently with different types of excipients, the selection of the proper excipients for a given formulation is a complex and challenging task. Some excipients may be effective in one formulation and cause protein degradation and aggregation in another.” This article contains a discussion on the types of stabilizing agent, and states that factors to be taken into account to choose the excipients include the complex physical and chemical degradation behaviour of proteins, and the potential multi-functional influences that each excipient can have on the biologic. Noting that the formulation scientist must possess a thorough knowledge of optimization of physical and chemical stability of the API for __________ Page 59 https://www.mhc.tn.gov.in/judis ( Uploaded on: 26/08/2025 07:59:11 pm ) rationally choosing the specific excipients and attaining optimal conditions for stability, the article concludes that excipient selection is a challenging task involving empirically strenuous efforts and resources.