API and IP Newsletter
Contents
FDA approvals
We follow FDA approvals of small molecules and analyse brief IP situation of the approved molecule. We study API synthetic routes.
Last month Reata sought approval for Omaveloxolone. Brand name Skyclarys, this is a medication used for the treatment of Friedreich's ataxia.
Friedreich ataxia (FA) is a rare inherited disease which causes progressive damage to nervous system and movement problems. FA is rare disease. However, still the most common form of hereditary ataxia in US, it affects about one in every 50,000 people.
The approved, Omaveloxolone is a semisynthetic triterpenoid. Synthesis of Omaveloxolone is reported in WO2013163344A1 from RTA 401 (Bardoxolone).
RTA 401 can be prepared according to the methods taught in prior art, for example, by Honda, et al., 1998; Honda et al., 2000b; Honda et al., 2002; Yates et al., 2007; and U.S. Pat. Nos. 6,326,507 and 6,974,801.
There is no relevant information about import of RTA 401 compound by Indian generic companies. Four crystalline forms (class 2, class 3, class 4 and class 5) and amorphous form are reported in patent literature.
Omaveloxolone has a pKa of 7.26 and is practically insoluble in water across the physiological pH range.
Capsule contents include croscarmellose sodium, magnesium stearate, pregelatinized starch, and silicified microcrystalline cellulose. The hard capsule shells contain FD&C Blue #1, ferric oxide yellow, hypromellose, titanium dioxide, and white ink.
Reata expects sales to peak at $1.2 billion.
General information
Schizophrenia Clinical Trials Pipeline Analysis: 60+ Companies are Working to Improve the Treatment Space
A snapshot of the Schizophrenia Pipeline Drugs
News here.
Duopharm to market Luye Pharma’s cholesterol management product in Malaysia
Duopharma Marketing will have exclusive rights to market and distribute a traditional Chinese medicine, developed by Luye Pharma for cholesterol management.
Luye Pharma has utilised modern technology to ferment special red yeast rice, said to be a natural alternative for cholesterol management.
The collaboration will enable Luye Pharma to leverage the long-term expertise of Duopharma Biotech in the cardiovascular therapeutic field.
News here
Intellectual Property
T 1349/21 – Decision by Appeal Board at EPO on patent related to low-alcohol beer.
This week I could not find any interesting case for pharma. In this write-up I covered the case related to patent which claims Alcohol free or low alcohol beverage having an alcohol content of not more than 1.0 %
The appeal was filed by the patent proprietor Anheuser-Busch InBev S.A. This is against the opposition division's decision to revoke EP 2804942.
The patent was opposed by Heineken Supply Chain B.V.
Claim 1 of the main request reads as follows:
"1. Alcohol free or low alcohol fermented malt-based beverage having an alcohol content of not more than 1.0 vol.%, preferably not more than 0.7 vol.%, comprising esters and higher alcohols defining a flavouring profile close to a lager beer, wherein a higher alcohol is an alcohol having a molecular weight higher than ethanol, characterized in that it comprises (a) 7.00-30.00 ppm ethyl acetate and (b) 0.01-0.20 ppm ethyl butyrate."
An alcohol-free or low-alcohol beer is referred to as an "NA beer".
Following are the prior art documents.
D8: US 6,162,260 A
D16: AU 2003 203 994 A1
D40: H.D.Belitz et al.: Food Chemistry, 4**(th)revised and extended edition, Springer-Verlag, 2009, pages 340, 902-906|
D57: Experimental report submitted by the appellant before the opposition division.
The closest prior art:
D8/D16 considered as the closest prior art.
D8/D16 (abstract) discloses a method for making a low-alcohol brew. Examples 6 and 7 of D8/D16 disclose two NA beers comprising 17 ppm ethyl acetate and 0.76% ethanol (example 6, table 8), and 15 ppm ethyl acetate and 0.5% ethanol (example 7, table 9).
Both NA beers are alcohol-free or low-alcohol fermented malt-based beverages and comprise the contents of alcohol and ethyl acetate required by claim 1 of the main requests, namely less than 1.0 vol.% alcohol and 7.00-30.00 ppm ethyl acetate.
The beers of examples 6 and 7 also comprise esters (isoamyl ester) and higher alcohols (amyl alcohols, isobutyl alcohol and isopropanol), as required by claim 1 of the main requests.
Distinguishing features
Examples 6 and 7 do not disclose the amount of ethyl butyrate.
Hence, the difference between the beverage of claim 1 of the main request and examples 6 or 7 of D8/D16 is the amount of ethyl butyrate required by claim 1 (0.01-0.20 ppm). This was common ground between the parties.
Technical effect and objective technical problem
Anheuser-Busch InBev S.A. relied on D57 for the formulation of the technical problem. It submitted that, according to the technical data in D57, the NA beers of inventive examples 1 and 2 of the patent performed better than all comparative examples in their overall likeness to alcoholic lager beer. The technical problem was therefore the provision of NA beers with a flavour profile close to that of a regular beer.
The board did not agree with Anheuser-Busch InBev S.A.’s submission. The board finds that, in D57, there is no fair comparison between examples 1 and 2 and the comparative examples of the patent for the following reasons.
Table 1 of D57 is reproduced below:
The beer compositions of examples 1 and 2 according to the patent (EX1 and EX2) each have an average overall score greater than that of the comparative beers (CEX6, CEX11, CEX12 CEX19 and CEX20).
However, the beer compositions of examples 1 and 2 according to the patent comprise amounts of ethyl acetate, isoamyl acetate, ethyl hexanoate and amyl alcohol which are different from the amounts of the corresponding compounds in the comparative beers.
Therefore, it is not merely through the distinguishing feature of claim 1 of the main request, i.e., the presence of 0.01-0.20 ppm ethyl butyrate, that the beer compositions of examples 1 and 2 according to the patent differ from the comparative beers.
Since ethyl acetate, isoamyl acetate, ethyl hexanoate and amyl alcohol are flavouring compounds of beer compositions, the average overall scores achieved by examples 1 and 2 of the patent must be assumed to be also linked to the presence and quantities of these additional compounds.
The scores cannot therefore be credibly attributed to the amount of ethyl butyrate alone. For that reason, the data in table 1 of D57 do not reflect a fair comparison between examples 1 and 2 of the patent and a beer representing examples 6 and 7 of D8/D16. This was not disputed by Anheuser-Busch InBev S.A
Therefore, the average scores for likeness to alcoholic lager beer found for examples 1 and 2 of D57 cannot be taken into consideration when formulating the objective technical problem.
For the above reasons, the objective technical problem can only be seen as the provision of an alternative NA beer.
Obviousness- decision by the Board
The selection of an amount of ethyl butyrate defined in claim 1 of the main request, in the absence of any effect, is arbitrary. Choosing an amount of ethyl butyrate as claimed is within the routine abilities of the skilled person and, for this reason alone, cannot support any inventive step. Therefore, inventive step must be denied in view of D8/D16 alone.
The amount of ethyl butyrate as claimed is moreover rendered obvious by document D40. D40 refers to aroma compounds. Table 20.7 on page 903 thereof mentions a content of ethyl butanoate (i.e., ethyl butyrate) of 0.01 mg/l in alcohol-free beer. This content corresponds to a content of 0.01 ppm, which is within the claimed range of 0.01 to 0.2 ppm. Thus, the solution proposed by claim 1 is also obvious in view of D8/D16 in combination with D40.
In view of the above, the board concludes that the subject-matter of claim 1 of the main request does not involve an inventive step.
The main request is not allowable. The patent was revoked. Decision here.
