API and IP Newsletter
Contents
Ivermectin Does Not Reduce Risk of Covid Hospitalization, Large Study Finds
Team creates new nanoplatform for delivering drugs into T cells
FDA approvals in March 2022
We follow FDA approvals of small molecules.
Ganaxoline: General information
Ganaxoline is approved in March 2022 under the brand name Ztalmy. It is a medication used to treat seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD).
Ztalmy (ganaxolone) oral suspension contains ganaxolone, a neuroactive steroid gammaaminobutyric acid A (GABAA) receptor positive modulator. Ganaxolone is a methyl-substituted (at the 3ß position) analog of the endogenous neurosteroid allopregnanolone, a derivative of progesterone.
Ganaxolone is a white to off-white crystalline powder that only exists in one crystal form and has low aqueous solubility.
Synthesis:
WO1993018053A1
Synthesis of ganaxolone is reported in U.S. Patent No. 5,319,115 (WO1993018053A1) and the literature (He et. al., Zhongguo Xinyao Zazhi (2005), 14(8),1025- 1026) wherein dione 2 is reacted with Corey's Reagent
WO2011019821A2
This family claims to provide a simple and cost effective method for the manufacture of ganaxolone from 5α-pregnane-3, 20-dione in example 6.
Indian scenario:
Surprisingly there is hardly any Indian active DMFs for progesterone or its derivatives. Symbiotic had filed DMF for progesterone four years ago. Though there are many Indian suppliers listed in various databases for progesterone API, these suppliers could be supplying to domestic and less regulated markets. This is to be verified.
General information
Ivermectin Does Not Reduce Risk of Covid Hospitalization, Large Study Finds
The anti-parasitic drug ivermectin, which has surged in popularity as an alternative treatment for Covid-19 despite a lack of strong research to back it up, showed no sign of alleviating the disease, according to results of a large clinical trial published on Wednesday.
The study, which compared more than 1,300 people infected with the coronavirus in Brazil who received either ivermectin or a placebo, effectively ruled out the drug as a treatment for Covid.
News here.
Team creates new nanoplatform for delivering drugs into T cells
The researchers performed an experimental study constructing a pH-sensitive delivery system into T cells and their subsets by using carboxy-terminal dendrimers (highly ordered, branched polymeric molecules) bearing phenylalanine (Phe) and hydrophobic acid anhydride (cyclohexanedicarboxylic anhydride, CHex), such as PAMAM-CHex-Phe and PAMAM-Phe-CHex. These dendrimers showed a higher association with splenocyte-derived T cells, which suggests that the hydrophobic effect significantly influences the association of dendrimers with immune cells.
News here.
Intellectual Property
T 2521/18 (Aerosol formulations/JAGOTEC)
This appeal filed at European Patent Office by the opponent Generic UK is directed against the opposition division's decision finding that European patent EP 2488158 in amended form met the requirements of the EPC.
The following document is cited as prior art
F1 (Prior art): WO 2005/034911
The patent had been granted with 20 claims. Here.
The Patentee’s (Jagotec’s) arguments, where relevant to the present decision, can be summarised as follows:
The subject-matter of claim 1 is novel.
The claim did not relate to a method of preparation, but concerned the use of DSCG (disodium cromoglycate) for forming floccules of micronised FF (formoterol fumarate dihydrate), FP (fluticasone propionate) and DSCG that had the same density as the HFA (hydrofluoroalkane) propellant.
F1 neither explicitly nor implicitly disclosed the formation of floccules, let alone the use of DSCG for forming such floccules.
The only disclosure in F1 regarding DSCG was that it protects the formulation against moisture. However, protection against moisture was unrelated to the formation of three-way floccules defined in claim 1.
Floccule formation required narrower concentration ranges of the components, especially DSCG, and achieved a particular stabilising effect of the aerosol formulations. Therefore, in accordance with the established case law (G 2/88), the use of claim 1 was novel.
The main difference between the disclosures of F1 and the patent is that the patent teaches that DSCG increases the stability of the aerosol suspensions not only by scavenging water but also by forming three-way floccules with FF and FP which match the average density of the propellant.
The opponent’s (Generic UK) view
The considered that the composition of the formulations in Example 1 of F1 and in Example 3 of the patent (i.e. according to claim 1) are practically the same and that they were prepared in essentially the same manner, the board is persuaded that three-way floccules according to claim 1 are also formed in Example 1 of F1.
This assumption is supported by the fact that both formulations showed high stability when tested at 40°C and 75% RH at 1, 3 and 6 months.
EPO case law distinguishes between two types of use claims
i) the use of a physical entity to achieve an effect, and
ii) the use of a physical entity to produce a product.
The opponent (Generic UK) considered that claim 1 was a type ii) claim, while the patentee (Jagotec) maintained that it belonged to type i).
The Appellate Board’s view
Having regard to the wording of claim 1 and the nature of its invention, the board agrees with Generic UK that claim 1 is a type ii) use claim: it relates to a process for the production of a product
Contrary to the patentee’s (Jagotec) view, the formation of three-way floccules defined in claim 1 cannot be considered as the achieving of an effect.
The floccules, which were already present in the aerosol suspension of Example 1 of F1, constitute a structural feature of the suspension. They contribute to the actual effect achieved, namely stabilising the formulation, but do not themselves constitute the achieving of a new effect.
According to both the patent and F1 (prior art), the effect brought about by DSCG is to increase the stability of the aerosol suspensions.
This is achieved by scavenging water. The patent's inventors observed that, in addition to scavenging water, DSCG also forms three-way floccules that match the average density of the propellant. However, the formation of floccules, rather than constituting a new effect, is an additional explanation of the mechanism of how DSCG exerts its stabilising effect.
Consequently, despite the purpose indicated in its wording, claim 1 is aimed at the preparation of a formulation.
It is established case law that the purpose mentioned in a claim to a process for the production of a product is not suitable for distinguishing the claimed process from other preparation processes carried out using identical features but for a different purpose.
Therefore the interpretation of claim 1 as being directed to a process for the preparation of a product leads to the conclusion that the purpose of forming three-way floccules having the average density of the propellant is merely descriptive and cannot render the claimed subject-matter novel.
Patent was revoked. Here.
