API and IP Newsletter
Contents
How the Indian Pharmaceutical Industry is planning to grow in 2022
Supreme Court: Pharma freebies for doctors' immoral or illegal
FDA approvals in January 2022
We analyse FDA approvals every month. FDA approved daridorexant (QUVIVIQ) in January 2022.
QUVIVIQ contains daridorexant, an orexin receptor antagonist. It is a medication used for the treatment of insomnia.
The chemical name of daridorexant hydrochloride is (S)-(2-(5-chloro-4-methyl-1H-benzo[d]imidazol-2-yl)-2-methylpyrrolidin-1-yl)(5 methoxy-2-(2H-1,2,3-triazol-2-yl)phenyl)methanone hydrochloride.
Daridorexant HCl is a white to light yellowish powder that is very slightly soluble in water.
The synthesis of daridorexant, is described in WO2013/182972 and W02015/083094. Crystalline salt forms of daridorexant are disclosed in WO2015/083071; and crystalline forms of daridorexant in free base form are disclosed in WO2015/083070.
Reference example (6) in WO2015/083071 represents synthesis of Daridorexant. Process described is as below.
(S)-5-chloro-4-methyl-2-(2-methylpyrrolidin-2-yl)-1 H-benzo[d]imidazole hydrochloride (62.8 g; 121 mmol) is dissolved in DCM (750 ml) followed by the addition of 5-methoxy-2-(2H-1 ,2,3- triazol-2-yl)benzoic acid (62.8 g; 121 mmol) and DIPEA (103 ml; 603 mmol). Stirring is continued for 10 minutes followed by the addition of HATU (47 g; 124 mmol). The reaction mixture is stirred for 16 hours at RT. The solvents are evaporated under reduced pressure and the residue is dissolved in EtOAc (1000 ml) and washed with water (3x 750 ml). The organic phase is dried over MgS04, filtered and the solvent is evaporated under reduced pressure. The residue is purified by CC with EtOAc / hexane = 2 / 1to give 36.68 g of the title compound as an amorphous white powder. tR [min] = 0.73; [M+H]+ = 450.96
In our assessment, 2-methylpyrrolidine-2-carboxylic acid is RM for the synthesis of daridorexant and Sai, Aurigene, Jubilant, Syngene importing it in small quantities, these companies must be in early stage of development of daridorent and perhaps could be in position to file DMFs in next 12-18 months.
General information
How the Indian Pharmaceutical Industry is planning to grow in 2022
Contributing immensely to global health, the Indian pharmaceutical industry by volume is the 3rd largest in the world. In (2021-2022) FY22, the pharmaceutical industry recorded a growth of 9-11 per cent which was mainly driven by a push from emerging and domestic markets. Going forward to 2022, it is expected that the Indian pharmaceutical industry will foster a culture of R&D and innovation to enable rapid drug discovery and development to improve the health outcomes of people worldwide.
News here.
Supreme Court: Pharma freebies for doctors 'immoral or illegal
The Supreme Court on Tuesday termed “immoral or illegal” the practice of pharmaceutical companies offering freebies to doctors, saying it affects common people by driving up healthcare costs.
The court reminded all stakeholders that such practices are “prohibited by law” and pharmaceutical companies are not entitled to any income tax exemption for the unethical expenses.
News here.
Intellectual Property
GSK vs Teva on Skinny label or label cave out issue
Section viii carve outs
What is Section viii carve outs in US?
The statute (21 U.S.C. § 355(j)(2)(A)(viii)) allows the generic sponsor to remove or “carve out” the protected indication or other protected condition of use from the product labelling, and submit a “section viii” statement explaining that the applicant does not seek approval for the protected use
Though statue looks simple the issues related to section viii carve-outs remain unresolved in the context of the small molecules.
This is the case of Carvedilol and GSK’s patent # `000 reissued in 2008, related to treatment of congestive heart failure post-myocardial infarction using carvedilol.
In lower court, Teva argued that it could not be found to have induced infringement because the patented use was carved out on the skinny label.
The lower Court held that GSK failed to prove Teva caused the direct infringement.
GSK appealed. On appeal, GSK argued that Teva promotes its generic product as being the same as the branded product.
In October 2021, a three-judge CAFC panel decided in favour of GSK.
The implications of this CAFC decision could be significant. This decision could create considerable risks for generic companies using skinny labels. Henceforth, the potential carve-out could be more difficult for any generic company to execute.
Noticing this, Teva filed a petition for rehearing en banc. A response to the petition was invited by the court. GSK responded. The court also accepted amicus briefs filed by Apotex, Association for Accessible Medicines; Mylan and few others.
What is petition for rehearing en banc?
In law, an en banc session is a session in which a case is heard before all the judges of a court rather than by one judge or a smaller panel of judges.
In this case, the Court decided not to rehear the matter en banc, over the dissenting opinions of three of the judges.
However, Judges commented equitable estoppel could remedy Teva’s concerns. In most cases, equitable estoppel serves as an absolute bar to a patentee’s infringement action.
Now, what is doctrine of Equitable estoppel?
When a person tries to take a legal action that would conflict with his previously given statements, claims or acts, this legal principle would prohibit him from doing so.
Teva alleged, GSK’s failure to communicate to Teva or FDA that the Post-MI LVD (congestive heart failure post-myocardial infarction) was an alleged infringing use of the ’000 patent led Teva to reasonably infer that GSK did not intend to enforce its patent against Teva for the use of carvedilol for Post-MI LVD.
The Judges allowed the district court to address these fairness concerns by adjudicating that defence on remand. If the result is unsatisfying, this Court will surely have a chance to review it.
These considerations on remand suggest that everything is not over yet for Teva and Gx on label carve out. We have to stay tuned. Decision here.
