API and IP Newsletter

 Contents



Paragraph IV patent certifications in last two months


The Food and Drug Administration (FDA) regularly publishes information relevant to 180-day exclusivity for generic drug applicants provided under section 505(j) of the Federal Food, Drug, and Cosmetic Act (FD&C Act). 


Generally, this list describes drug products for which one or more substantially complete abbreviated new drug applications (ANDAs) containing a “paragraph IV” (PIV) patent certification have been submitted to FDA.


However, this list does not state names of ANDA filers with PIV certificate and one must rely on an educated guess based on the public domain information. If Brand sues the Gx, then of course it is known who has filed ANDA with P-IV certificate, but till then it will be a guess work.


Drug Name

Dosage Form

Strength

RLD/

NDA

Submission

No of ANDAs

SIDVIM comments

Cannabidiol

Oral Solution     

100 mg/mL

Epidiolex

28 September 2022

10

NCE-1 date was on 28 September 2022 and 10 filers were there on NCE-1 date. GW Pharmaceuticals reported Epidiolex sales of $296 million in first year. So might not be huge market, and 10 Gxs are competing for the small share

Emtricitabine and Tenofovir Alafenamide Fumarate

Tablets

120 mg/15 mg

Descovy

31 October 2022

1

This ANDA filing is for 120mg/15 mg. Six ANDA's were already filed for 200 mg/25 mg Descovy. 

This 120 mg/25 mg strength was approved in January 2022, and one of these 6 ANDA filers must have quickly filed ANDA on the new strength, to be able to qualify for 180 D exclusivity on this new strength.

Levo-thyroxine Sodium

Capsules

137 mcg and 

Tirosint 

04 November 2022

1

Levothyroxine Sodium capsule, there are several strenghths approved. Teva had earlier sought approval for 0.2 MG capsule and there is high likelihood that this ANDA also could have been filed by Teva.

Levothyroxine Sodium

Oral Solution

13 mcg/mL 

Tirosint-Sol

30 September 2022

1

Many Gx companies are active. Mylan and Azurity had earlier sought approvals for 150 mcg/5 ml and 100 mcg/5 ml respectively. One can expect Mylan could file ANDA for oral solutions for various strengths. 

25 mcg/mL 

50 mcg/mL 

75 mcg/mL 

88 mcg/mL

100 mcg/mL

112 mcg/mL

125 mcg/mL

137 mcg/mL

150 mcg/mL

175 mcg/mL

200 mcg/mL

Olaparib

Tablets

100 mg and 150 mg

Lynparza

01 November 2022

1

There are about 6 DMFs filed by Cipla, Hetero, DRL, Alembic etc., anyone of them is capable of filing ANDA. However, we noticed Teva had opposed FDF patent at EPO. Hence Teva could be using the same FDF strategy for US.  

Raltegravir Potassium

Tablets          

600 mg

Isentress HD

21 October 2022

1

There was earlier filing of 400 mg, this ANDA filing is for Isentress HD 600 mg. In import export database one could notice Mylan is exporting 600 mg tablets to US, might be for seeking MA. There could high possibility that this ANDA is filed by Mylan. It is interesting to note Mylan filed two DMFs for two different processes. Mylan is one among other five DMF filers. 

Tiopronin

Delayed-release Tablets

100 mg and 300 mg

Thiola EC

11 October 2022

2

Teva and Par have already approvals for tablets they also could have filed ANDA for DR tablets. Biophore and MSN have filed DMFs and Teva could be using API either from Biophore or from MSN. 

Spring Pharmaceuticals was also litigating with Brand on anti-trust issues for Thiola and as a remote possibility Spring also could have developed Thiola EC and had filed ANDA.

As per import export database MSN seems to be very active in API and impurity supply to many Gx companies. Hence, Teva could be using MSN’s API, which was filed in October 2017. 

https://www.fda.gov/media/133240/download


General information


Leveraging Artificial Intelligence and Human Know-How to Accelerate Drug Discovery


Through the integration of human expertise, artificial intelligence, and automation robotics, bio/pharma companies can more efficiently target drug discovery efforts with bigger payoff.

Astellas’ R&D is often focused on therapeutic drugs for rare diseases with small patient populations, presenting challenges to sample collection and limiting the potential for drug discovery through traditional approaches. Against this backdrop, a solution came to light with the advent of technology that utilizes induced pluripotent stem cells (iPSCs) to differentiate cells into target cells


News here.


PrecisionLife Enters Multi-Target R&D Partnership with Ono Pharmaceutical


PrecisionLife Limited, a global techbio company generating insights into disease biology to create novel precision medicines in chronic diseases, has entered into a multi-target discovery and validation partnership with Ono Pharmaceutical Co., Ltd., an R&D-orientated pharmaceutical company.
 
The R&D collaboration will leverage PrecisionLife’s combinatorial analytics-generated insights to identify novel therapeutic targets and patient stratification biomarkers in central nervous system (CNS) disorders for development by Ono.


News here.



Intellectual Property 


Takeda Pharmaceutical Company Limited vs Generics (UK) Ltd (brigatinib)

 

The decision under appeal because the opposition division rejected the opposition filed against EP 2300013 by Generics UK.

 

Generics UK appealed. 

 

This is composition of matter patent of brigatinib. Markush claim. 

Figure imgb0054


The patent was opposed on the grounds of Article 100(a), for lack of inventive step, 100(b) and 100(c) EPC.

 

In the appealed decision, the opposition division concluded that the patent as granted did not add subject-matter. Furthermore, the claimed subject-matter was sufficiently disclosed and involved an inventive step starting from document D8 (WO 2004/080980 A1) as the closest prior art.


Generics UK Limited’s arguments relevant to the present decision were as follows.

  1. Document D8 is the closest prior art. 

  2. The application as filed did not credibly show that brigatinib was an ALK inhibitor; the test results on page 235 neither included brigatinib nor demonstrated a structure-activity relationship allowing the conclusion that brigatinib was an ALK inhibitor. 

  3. A structural modification of the compounds shown to be active would disrupt biological activity.

  4. Therefore, no technical effect could be acknowledged for brigatinib and the objective technical problem had to be defined as the provision of further compounds. Brigatinib was merely an arbitrary compound.

 

Takeda’s arguments were as follows.

  1. Starting from D8 as the closest prior art, the subject-matter of the main request differed in the structure of brigatinib. 

  2. The technical effect provided by this difference was the inhibition of ALK. 

  3. The effect had been credibly demonstrated by the structure-activity relationship derivable from the ALK inhibitors disclosed on page 235 of the application as filed.

  4. Therefore, the objective technical problem was the provision of alternative kinase inhibitors, in particular ALK inhibitors, for the treatment of cancer. Generic UK had not disputed that brigatinib was a non-obvious solution to this problem.

  5. Therefore, the results presented on page 235 provide (indirect) evidence that R2 4-(4-methylpiperazin-1-yl) piperidin-1-yl, which did not impair activity, will also be non-detrimental when structure would comprise dimethylphosphoryl, as in brigatinib.

 

The board therefore upheld that, contrary to the Generics UK’s view, the experimental results in the application as filed demonstrate a structure-activity relationship which allows the conclusion that brigatinib is an ALK inhibitor.

 

The problem can then be formulated as the provision of an alternative ALK inhibitor.

On the basis of the board's conclusion, Generics UK  accepted that the experimental results in the application as filed made it credible that brigatinib is an ALK inhibitor, and that brigatinib was not an obvious solution to the technical problem of providing an alternative ALK inhibitor starting from the disclosure of document D8. It did not, therefore, raise any argument in this respect.

 

The board opined that brigatinib is a non-obvious solution to the skilled person seeking alternative ALK inhibitors, since there is no hint in D8 of the modifications required to arrive at brigatinib, a new ALK inhibitor.


Patent was upheld. 

Decision here.











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