API and IP Newsletter
Contents
Pfizer Sues MSN Labs to Block Copies of Xeljanz Arthritis Drug
Pfizer plans $120m investment for Covid-19 oral drug manufacturing in US
DMFs filed by Biophore
We follow DMF filings by Indian companies. Below is an analysis of a few DMFs filed by Biophore.
Conclusions:
Biophore is very innovative in product selection.
The present strategy seems to be to target imaging agents, APIs, for diagnostics.
Target niche molecules, small molecules, and enter into a market where there is limited or no competition.
On the chemistry front, Biophore selects molecules which are difficult to develop and manufacture.
General information
Pfizer Sues MSN Labs to Block Copies of Xeljanz Arthritis Drug
Pfizer Inc. alleges that MSN Laboratories Private Ltd.’s proposed generic versions of Xeljanz tablets (tofacitinib citrate) and oral solution infringe a patent for the blockbuster arthritis drug, according to a federal lawsuit in Delaware.
MSN Labs wants to sell copies of Xeljanz’s twice-daily 5- and 10-milligram tablets and of its twice-daily oral solution, according to a complaint filed Monday in the US District Court for the District of Delaware. Pfizer seeks court orders blocking the copies until the patent has expired.
News here.
Pfizer plans $120m investment for Covid-19 oral drug manufacturing in US
Pfizer has announced plans to invest $120m in its manufacturing facility in Kalamazoo, Michigan, US, to produce its Covid-19 oral drug, Paxlovid (nirmatrelvir [PF-07321332] tablets and ritonavir tablets).
The new investment will help in expanding the active pharmaceutical ingredient (API) and registered starting materials (RSMs) production.
News here.
Intellectual Property
T 1805/17 () of 1.6.2022: Process for preparing oxycodone hydrochloride
Oxycodone is big market worldwide. I don’t have sale of oxycodone HCl in Europe but WW sale is over $ 5 Bn with reasonably good growth potential. Here
This was regarding EP2314589A1 applicant is EURO-CELTIQUE S.A. The application relates to Process for preparing oxycodone hydrochloride having less than 25ppm 14-hydroxycodeinone.
The examination division refused the application and hence matter was under appeal.
The following documents inter alia were cited in examination proceedings:
D1: WO 2004/016618 A1
D2: Krabetanig et al., Arch. Pharm. Pharm. Med.Chem., 329, 325-326 (1996)
D3: US 7,906,647
D4: Experimental report from parallel proceedings in relation to European patent 2 305 683
D5: Declaration of Prof. Lamprecht dated 11 July 0216
D6: Summons to oral proceedings in EP 2 305 683
D7: Declaration of Prof. Diederichsen dated 16 July 2017
D8: US 6,008,355
D9: Coop et al., Tetrahedron 55(1999) 11429-11436
The sole independent claim 1 of the main request reads as follows:
"1. A process for preparing an oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone as determined by the HPLC method of Example 6, which process comprises the steps of:
(a) hydrogenating a 14-hydroxycodeinone composition to obtain an oxycodone free base composition;
(b) converting the oxycodone free base to oxycodone hydrochloride; and
(c) hydrogenating the oxycodone hydrochloride composition formed in step (b) to produce an oxycodone hydrochloride composition having less than 25 ppm 14-hydroxycodeinone."
The closest prior art considered by examining board was D1.
It discloses the preparation of various polymorphs of oxycodone HCl. Since oxycodone HCl is the product of contested claim 1, the board also agrees that D1 can represent the closest prior art.
Problem to be solved. According to the contested decision by examining board, the objective technical problem was the provision of an alternative process for the preparation of oxycodone HCl.
In appeal proceeding patentee argued, there is no pointer nor motivation in D1 nor in D2 which would lead the skilled person to the conclusion that the above-mentioned problem could be solved by the implementation of a step (c) as claimed.
The patentee said, D1 does not address the issue at all. D2 on the other hand merely describes the catalytic hydrogenation of 14-hydroxycodeinone to oxycodone free base and does not disclose the preparation of oxycodone HCl. Furthermore, patentee stated, it would be counter-intuitive for the skilled person to consider the purification of a compound using the same method by which it was produced, namely hydrogenation.
The examining division arrived at the conclusion that the claimed subject-matter lacked inventive step over D1 in combination with D2. However, this conclusion was reached starting from an objective technical problem formulated as the provision of an alternative process, and the view that step (c) was merely an arbitrary and thus obvious modification of an otherwise known process .
A further ground for denial of inventive step according to the contested decision was based on the fact that claim 1 at issue was exclusively directed to a process for preparing an oxycodone HCl composition starting from 14-hydroxycodeinone, and did not specify the manner in which the latter was prepared.
The description on the other hand taught that unwanted 8,14-dihydroxy-7,8-dihydrocodeinone, and therefore 14-hydroxycodeinone in the product oxycodone HCl, was obtained exclusively in the oxidation of thebaine to prepare 14-hydroxycodeinone.
However, other syntheses of oxycodone starting from codeine or codeinone were known. Since these alternative routes may not have yielded 8,14-dihydroxy-7,8-dihydrocodeinone as an impurity in the preparation of 14-hydroxycodeinone at all, the examining division reasoned, claim 1 at issue did not address the problem associated with the formation of an impurity during the oxidation of thebaine.
The board understood the argument set out in the contested decision as follows:
when 14-hydroxycodeinone is prepared from codeine or codeinone, i.e. a starting material other than thebaine, the problem associated with a 8,14-dihydroxy-7,8-dihydrocodeinone impurity does not arise.
In such a process, step (c) would be futile, since unwanted 14-hydroxycodeinone would not be produced in the preparation of oxycodone HCl.
For such a process therefore, the objective technical problem would be the provision of an alternative process to the conventional process (comprising steps (a) and (b) of claim 1 at issue) for preparing oxycodone HCl.
The solution, the addition of a second hydrogenation in step (c), would be arbitrary and therefore lack inventive step.
The board did not agree with this approach.
Firstly, it is set out in the application that oxycodone HCl prepared by known procedures has a 14-hydroxycodeinone level of greater than 100 ppm.
This is further confirmed by post-published patent D3, as well as the fact that none of the cited prior art disclose oxycodone HCl having a lower level.
If all known procedures lead to oxycodone HCl with such high levels of 14-hydroxycodeinone, it would appear reasonable to assume that similar issues with the generation of 8,14-dihydroxy-7,8-dihydrocodeinone would occur also in the processes to produce 14-hydroxycodeinone from codeine or codeinone mentioned in the application.
Indeed, if this were not the case, one would have expected that the problem of unwanted 14-hydroxycodeinone could simply have been solved in the prior art by using a starting material different from thebaine.
However, since D3 states that oxycodone HCl prepared by all known procedures has 14-hydroxycodeinone levels above 100 ppm, this does not appear to have been possible.
Secondly, this conclusion is supported by the arguments of the Patentee. The patentee analysed the prior art relating to the preparation of 14-hydroxycodeinone from codeinone, namely D8 and D9. As noted by the patentee and stated in expert declaration D7 (section H), 14-hydroxycodeinone prepared according to these documents will inevitably also contain 8,14-dihydroxy-7,8-dihydrocodeinone.
The board formulated the objective technical problem as the provision of a process for the preparation of oxycodone HCl with a lower 14-hydroxycodeinone content, independently of whether the starting material is thebaine, codeine or codeinone. The conclusions under obviousness must be based on this newly formulated objective technical problem.
Hence in appeal, the decision of examining division was set aside. It was agreed by the appeal board that subject-matter of the claims of the main request involves an inventive step.
The case was remitted to the examining division with the order to grant the patent. Decision here.
