API and IP Newsletter
Contents
EC announces proposals for pharma reforms that cuts market exclusivity
Hatch-Waxman Defendants May Develop Non-Infringement Defenses Beyond Their Notice Letters
DMFs filed in February 2023
FDA publishes a quarterly list of DMFs filed by various API manufacturers. We analyse those. Type II DMFs. We study DMFs filed by Indian companies.
In the month of February, about 63 DMFs were filed, and 40% of those were Indians. Some of our observations are as below.
General information
EC announces proposals for pharma reforms that cuts market exclusivity
Three options were assessed for data exclusivity, all of which are complemented by a set of common elements:
Option A maintains the current system of regulatory protection for innovative (originator) medicines (8 years data + 2 years market protection) and adds 1 year of protection for products addressing unmet medical need and 6 months for comparative clinical trials.
Option B provides 6 years data + 2 years market protection for all innovative medicines. It adds an extra 2 years of regulatory protection for medicines addressing unmet medical needs or demonstrating no return on investment.
Option C provides for a variable duration of regulatory protection combined with obligations. Regulatory protection for originator products is split into standard and conditional periods. The standard period is 6 years of data + 2 years of market protection which can be extended by a (dependent) period of 1 or 2 years if the product is made accessible in all Member States. The protection can be also extended by 1 year for originator medicines addressing an unmet medical need and by 6 months for comparative trials. Incentives can be combined but cannot exceed current (8+2 years) regulatory protection.
News here.
Hatch-Waxman Defendants May Develop Non-Infringement Defenses Beyond Their Notice Letters
The court found that "it possesses no authority to penalise any perceived deficiencies in Mylan's Paragraph IV notice letter under the Hatch-Waxman Act" and, as a result, "it will not limit Mylan to the theories raised therein." As such, "Mylan may develop its non-infringement contentions in the ordinary course of this litigation."
Now generic companies retain the flexibility to develop those invalidity and non-infringement defences during litigation – and add additional defences – that may extend beyond what they put in their notice letters.
News here
Intellectual Property
Why endoxifen composition patent is not inventive as per EPO?
EP 2101731 was granted on the basis of eleven claims and issued to Jina Pharmaceuticals Inc.
Independent claim 1 as granted as follows
"A composition comprising an effective amount of a complex comprising synthetic endoxifen, wherein said endoxifen is a free base or is in the form of a salt for use in the treatment or prevention of cancer."
Two oppositions (Besins Healthcare Monaco and Bayer) had been filed against the grant of the patent on the grounds that its subject-matter lacked novelty and inventive step, that the claimed invention was not sufficiently disclosed and that the patent comprised subject-matter extending beyond the content of the application as filed. The patent proprietor ie Jina had filed the appeal against the decision of the opposition division to revoke the patent. This matter was before Board of Appeals.
This is very lengthy decision and there are several auxiliary requests filed during opposition proceedings. We will discuss only inventive step in this write-up for the main request.
Closest prior art
Document E1 (E1: Johnson et al.; Breast Cancer Research and Treatment, 85: 151-159 (2004) ) reports results of in vitro assays for estrogen receptor binding, inhibition of estrogen stimulated breast cancer cell proliferation and regulation of estrogen responsive genes indicating that endoxifen has equivalent activity to 4-OH-Tam, which is known as a potent active tamoxifen metabolite.
The identification of document E1 as an appropriate starting point in the prior art was not in dispute.
Problem to be solved
Document E1 does not describe a composition for use in the treatment or prevention of cancer by the oral mode of administration as defined in claim 1 of the main request.
The patent presents in example 10, results of in vitro experiments which are in line with the results from the experiments already described in document E1. In example 9 the patent further reports that mice can survive exposure to certain doses of intravenously administered endoxifen, whilst examples 11-15 relate to protocols for testing the effects of endoxifen following oral administration without presentation of any actual results.
In view of document E1 and having regard to the teaching in the patent the Board considers the objective technical problem as the provision of an effective and convenient administration form for endoxifen in the treatment of cancer.
Assessment of the solution
In view of the pharmacological activity of endoxifen as known from document E1 and taking account of the well-known convenience of oral administration the Board considers that the skilled person would, in the absence of any prejudice against oral administration of endoxifen, regard the claimed subject-matter an obvious solution for providing a convenient and effective mode of administration for endoxifen in the treatment of cancer.
In this context the Board observed that endoxifen represents one of various known metabolites of tamoxifen.
In accordance with the established jurisprudence a technical prejudice concerns an opinion or preconceived idea widely or universally held by experts in the relevant field. The existence of a prejudice relied upon for meeting the requirement of inventive step needs to be convincingly demonstrated by the proprietor, typically by reference to the literature or to encyclopedias published before the relevant filing date
The patentee relied with reference to the declaration in document E26 (Declaration by A. Ahmad of 24 December 2019) on the existence of a prejudice against effective oral administration of endoxifen.
In view of the common knowledge presented in document E27 (Drug Absorption Pharmacokinetics: 2015 Merck Manual Professional) the skilled person would already expect reduced absorption for endoxifen as compared to the more lipophile tamoxifen.
The prejudice would in particular follow from the known unsuitability for oral administration of the closely related tamoxifen metabolite 4-OH-Tam due to its inactivation by the liver as described in documents E8 (Pujol et al.; Cancer Chemother. Pharmacol., 36: 493-498 (1995)) and E30 (Mauvais-Jarvis et al.; Cancer Res., 46:1521-1525 (1986)), the structural similarity between 4-OH-Tam and endoxifen and the known inactivation of 4-OH-Tam and endoxifen by glucuronidation as described in document E31 (Zheng et al.; Drug Metabolism and Disposition, 35(10): 1942-48 (2007)) and cited in the review on first-pass glucuronidation of phenolics as a barrier to oral bioavailability of phenolics in document E28 (Wu et al.; J. Pharm. Sci., 100(9): 2001 3655-3681 (2011))
The Board observes, however, that the unsuitability of the tamoxifen metabolite 4-OH-Tam for effective oral administration due to extensive hepatic inactivation and elimination as reported in documents E8 (see page 497, left column, third full paragraph) and E30 (see page 1525, left column, last paragraph) may support the prejudice against oral administration of 4-OH-Tam, but does not necessarily demonstrate the existence of a similar prejudice with respect to endoxifen.
Accordingly, the Board concludes that the subject-matter of claim 1 of the main request does not involve an inventive step.
Decision here
