In Amgen Inc. v. Assistant Controller of Patents, the Madras High Court set aside the refusal of Amgen\u2019s patent application for \u201cLyophilized Therapeutic Peptibody Formulations\u201d. The application had been rejected on grounds of lack of inventive step under Section 2(1)(ja), non-patentability under Sections 3(d) and 3(e), and insufficiency of disclosure under Section 10(4) of the Indian Patents Act, 1970. The Court found these objections unsustainable and directed the application to proceed to grant, subject to claim amendments.<\/p>\n
Amgen\u2019s application (No. 5857\/CHENP\/2008) related to lyophilized formulations of romiplostim, a thrombopoietin receptor agonist (TPO-RA) peptibody that stimulates platelet production. The formulations improved romiplostim\u2019s stability by combining it with four specific excipients at defined concentrations.<\/p>\n
The application was rejected by order dated 31 March 2023 based on objections under Sections 3(d) and 3(e), lack of inventive step, and a pre-grant opposition raising concerns of obviousness, non-patentability, and insufficiency of disclosure.<\/p>\n
Amgen argued that the Controller\u2019s rejection under Section 3(d) was misplaced, as the method for preparing the lyophilized peptibody was not a mere use of a known lyophilization process. Regarding Section 3(e), Amgen contended that the composition exhibited synergy between the peptibody and excipients, as evidenced by Tables 40 and 41, which demonstrated enhanced stability. They further submitted that the comparative pre- and post-lyophilization data were not required to prove synergy, contrary to the Controller\u2019s objections. On sufficiency, Amgen maintained that providing experimental data for a single representative peptibody (SEQ ID 1017) satisfied disclosure requirements, and it was unnecessary to provide data for all 52 claimed mimetics. On inventive step, they pointed out that prior art did not disclose a lyophilized peptibody formulation, nor would a skilled person be motivated to combine the references to arrive at the invention.<\/p>\n
In response, the Assistant Controller contended that the claimed method was simply the application of a known lyophilization process to a peptibody already disclosed in prior art D4. He maintained that the excipients were standard in protein formulations, and that the data in Tables 40 and 41 was insufficient to demonstrate inventive step or synergy. Regarding sufficiency, the Controller noted that Formula V encompassed 52 peptide mimetics, but experimental data was provided only for SEQ ID 1017, rendering the disclosure inadequate under Section 10. Furthermore, in the absence of comparative pre- and post-lyophilization stability data, the Controller argued that synergy had not been established, and that the invention fell within the exclusion under Section 3(e).<\/p>\n
The Court observed that while prior art D4 disclosed a therapeutic peptibody of Formula V and mentioned lyophilization in general terms, it did not teach the specific method of lyophilizing the therapeutic peptibody of Formula V with the claimed excipients at defined concentrations. Therefore, the Court concluded that the method for preparing the lyophilized peptibody could not be considered a mere use of a known process, and the rejection under Section 3(d) was unsustainable.<\/p>\n
The Court rejected the objection under Section 3(e), affirming that Tables 39\u201341 adequately demonstrated synergy between the peptibody and excipients. It found the Controller\u2019s reliance on the absence of pre- and post-lyophilization data irrelevant, noting that the invention sought to enhance the stability of the therapeutic peptibody through lyophilization, not to increase protein concentration.<\/p>\n
The Court observed that although lyophilization and the use of excipients are generally known, the specific combination and concentrations claimed for the TPO peptibody were not disclosed in the prior art. Noting that excipient selection is highly protein-specific and requires empirical optimization, the Court concluded that the claimed formulation could not have been derived without hindsight and therefore involved an inventive step.<\/p>\n
The Court found that sufficiency under Section 10 was only partly satisfied. It observed that the although Formula V encompassed 52 TPO mimetic peptide sequences, the specification provided experimental data only for a peptibody containing SEQ ID No.1017. While this data enabled a skilled person to prepare formulations based on SEQ ID No.1017 and closely related mimetics, it did not provide sufficient guidance for the remaining 51 sequences. To reflect the actual scope of the disclosure, Formula V was restricted to SEQ ID No.459 (the 14\u2013amino acid core sequence shared by SEQ ID Nos.1012\u20131017), thereby narrowing independent claims 1 and 9 to sequences actually supported by the specification.<\/p>\n
The Court allowed Amgen\u2019s appeal, set aside the Controller\u2019s order, and directed the patent application to proceed to grant, subject to amendments to independent claims 1 and 9.<\/p>\n
wherein said pH buffering agent is 10 mM histidine and wherein the pH is 5.0;<\/em><\/p>\n wherein said bulking agent is 4% w\/v mannitol;<\/em><\/p>\n wherein said stabilizing agent is 2% w\/v sucrose;<\/em><\/p>\n wherein said surfactant is 0.004% w\/v polysorbate-20;<\/em><\/p>\n wherein said therapeutic peptibody comprises a structure set out in Formula V Formula V:[F\u00b9-(L\u00b9)e-P1-(L2)f-P2]-(L1)c-WSPd wherein:<\/em><\/p>\n F1 is an Fc domain attached at the N- terminus of -L1-P1-L2-P2;<\/em><\/p>\n P1 and P2 consist of peptides with the amino acid sequence of SEQ ID NO.459 of Table 6<\/em><\/strong>;<\/em><\/p>\n L1 and L2 are each independently linkers; e and d are each 0; and e and f are each independently 0 or 1.<\/em><\/p>\n \u2026\u2026.<\/em><\/p>\n wherein said pH buffering agent is 10mM histidine and pH is 5.0;<\/em><\/p>\n wherein said bulking agent is 4% w\/v mannitol;<\/em><\/p>\n wherein said stabilizing agent is 2% w\/v sucrose; and wherein said surfactant is 0.004% w\/v polysorbate-20; and<\/em><\/p>\n b) lyophilizing said therapeutic peptibody solution;<\/em><\/p>\n wherein said therapeutic peptibody comprises a structure set out in Formula V Formula V: [F1-(L1)e-P1-(L2)f- (L1)c-WSPd wherein:<\/em><\/p>\n F1 is an Fc domain attached at the N- terminus of -L’-P’-L2-P2;<\/em><\/p>\n P1 and P2 consist of peptides with the amino acid sequence of SEQ ID NO.459 of Table 6<\/strong>;<\/em><\/p>\n\n