API and IP Newsletter

 Contents

• DMFs filed by Divis Laboratories

• General information

• Novartis' Sandoz sells Chinese finished drugs plant to CDMO Jiuzhou for $15.1M

• Olon Expands On Multiple Fronts

• Intellectual Property

DMFs filed by Divis Laboratories

We analyse DMFs filed by various Indian companies. This time we had a look at DMF list of Divis. Some of our observations are as below. 

SUBMIT DATE	SUBJECT	Sidvim Comments
1/27/2022	TICAGRELOR	There are more than 30 DMFs. Price will be very competitive. Moving to south every quarter. It will settle near $ 600-700/Kg.
4/30/2021	ORLISTAT	Crowded market, 10 other DMFs, however, this seems to be innovator business for Divis. As per import-export database Divis is exporting to GSK at much higher price realisation than competitors.
3/9/2021	LACOSAMIDE	Too many players 28 DMFs. Divis seems to be sending free customer samples to Yoshindo, Kyowa, Nissin, Takeda, Nippon. Divis must be eyeing Japanies market.
7/29/2017	VIGABATRIN USP	MSN has dominated the market. It is USD 700-800/Kg product. Other 7 DMFs have already filed.
8/1/2016	PREGABALIN (ALTERNATIVE PROCESS)	Too many players, very crowded market 40 DMFs. But Divis has increased the capacity and Pregabalin, Mesalamine, these products are growing, Divis have 20%-30% of the market share and wishes  to achieve 60%-70% of the market as per their one of the earning call in 2021
1/8/2016	LEVETIRACETAM (PROCESS B)	There are about 29 DMFs, but Divis must be one of the world's largest manufacture of levetiracetam.

General comments

1. Divis targets innovator business

2. Divis eyes markets which are not approached by competitors, such as Japan market for specific products.

3. Selects products where they could achieve economy of scale. 

General information

Novartis' Sandoz sells Chinese finished drugs plant to CDMO Jiuzhou for $15.1M

Chinese CDMO Jiuzhou Pharmaceutical said it plans to buy a Sandoz finished drugs plant in Zhongshan in southern China for $15.1 million

News here.

Olon Expands On Multiple Fronts

Italian API and CDMO specialist Olon is expanding its high-potency capabilities at a site in India, at the same time as unveiling plans to invest a further €30m in a domestic biotech hub.

News here.

Intellectual Property 

Aptiom: Bial Vs Alkem-Delaware Court decision

Aptiom (eslicarbazepine acetate) is about $300 mio product in US. Alkem, DRL, Hetero, Jubilant, Torrent, Shanghai Zhongxi, Lupin and Apotex are known P-IV filers. DRL received approval, but there is no generic available in US market yet. 

Alkem has submitted ANDA No. 211199, seeking approval to engage in the commercial manufacture, use, sale, and/or importation of eslicarbazepine acetate tablets in 200, 400, 600, and 800 mg dosage forms.

Bial has asserted 6 claims across 5 patents in OB.

The #287, #354, and #536 Patents "once-daily patents."  The once-daily patents are directed to administering eslicarbazepine acetate once-daily to treat partial-onset seizures. Bial asserts infringement of claim 3 of the #287 patent.

The independent claim 1 of the #287 patent reads: A method for treating a patient with partial-onset seizures comprising administering once-daily about 1,200 mg of eslicarbazepine acetate to the patient, wherein the patient is a human.

Bial asserted infringement of claim 5 of the #354 patent. The independent claim 1 of the #354 patent reads: A method for treating a patient with partial-onset seizures, comprising administering once-daily from about 800 mg to about 1800 mg of eslicarbazepine acetate to the patient, wherein the patient is a human.

Bial asserted infringement of claims 7 and 8 of the #536 patent. The patent relates to a method for treating a patient with partial-onset seizures, comprising: administering once-daily to a patient in need thereof a pharmaceutical composition consisting essentially of eslicarbazepine acetate, wherein the oncedaily administration is pharmacologically effective to treat partial-onset seizures in the patient, and wherein the patient is a human.

Bial asserted infringement of claim 20 of the #954 patent. A method for treating an intractable epilepsy condition comprising administering to a subject in need thereof a therapeutically effective amount of eslicarbazepine or eslicarbazepine acetate wherein the subject has previously been treated with oxcarbazepine, and wherein the eslicarbazepine or eslicarbazepine acetate is administered as a monotherapy for treating said condition.

In this document, we will briefly cover pharmaceutical composition patent, ie #781. 

The claim 1 of the #781 patent reads: A pharmaceutical composition consisting essentially of eslicarbazepine acetate in combination with a binder and a disintegrant, wherein eslicarbazepine acetate is present in an amount of from 80 to 90 wt%, the binder is present in an amount of from 3 to 10 wt%, and the disintegrant is present in an amount of from 3 to 10 wt%, and wherein the pharmaceutical composition exhibits a dissolution of at least about 60% at about 30 minutes at a temperature of 37±0.5° C and a pH of about 4.5 using a paddle apparatus at a speed of about 100 rpm.

Claim 17 depends on from claim 1 and reads: "The pharmaceutical composition of claim 1, further comprising a lubricant, and/or glidant."

Bial asserted this claim 17. 

1. Almeida 2003 was published in 2003 and qualifies as prior art to the #781 patent.  The Patent Office was not made aware of Almeida 2003 during the prosecution of the #781 patent.

2. Almeida 2003 discloses the results of a Phase 1 "single-dose study" where healthy volunteers were administered a "single dose" of eslicarbazepine acetate. Almeida 2003 discusses the use of tablets with lower doses, and presumedly multiple tablets were administered at once to achieve the required dose. 

3. Following Almeida, the Judge came to the conclusion that Alkem has shown by clear and convincing evidence that an artisan of ordinary skill would have had a reasonable expectation of success in creating the formulation described in claim 17 of the #781 patent.

The summary of the decision on other patents is as below.

Patent No	Patent Expiration	Court decision
8372431	04/17/2030	Not asserted. Not the part of the litigation.
9206135	04/21/2026	Not asserted. Not the part of the litigation.
9566244	10/23/2028	Not asserted. Not the part of the litigation.
9643929	04/21/2026	Not asserted. Not the part of the litigation.
9750747	08/24/2032	Not asserted. Not the part of the litigation.
9763954	09/13/2028	Alkem will not induce infringement of claim 20 of the #954 patent. Alkem has established that claim 20 of the #954 patent is invalid under§ 112
10675287	05/06/2025	This is upheld. The Court said, Alkem has not established that claim 3 of the #287 patent is invalid
10695354	05/06/2025	This is upheld. The Court said, Alkem has not established that claim 5 of the #354 patent is invalid
10702536	05/06/2025	This is upheld. The Court said, Alkem has not established claims 7 and 8 of the #536 patent are invalid
10912781	10/23/2028	The Court said Alkem's ANDA will infringe claim 17 of the #781 patent. However, claim 17 of the #781 patent is invalid.
11364247	05/06/2025	Not asserted. Not the part of the litigation.

From this Delaware Court decision, Alkem must wait till May 2025 before generic launch. Let us see whether they would appeal against this decision. Here