API and IP Newsletter

Contents

• DMF filings in the month of June 2023

• General information

• Mallinckrodt to Go Bankrupt for Second Time in Three Years

• A novel approach to boost drug development in paediatric oncology

• Intellectual Property

• Delaware district court found Lonsurf patent valid and infringed

DMF filings in the month of June 2023

We follow DMF filings by Indian companies. One of the trends which is very visible in recent past is percentage of DMF filings by Indian companies is going down. Out of total 56 DMFs filed in the month of June 2023, almost 50% are from Chinese companies and about 25% are from Indian companies. 

 

HOLDER	SUBJECT	Sidvim Comments
HONOUR LAB LTD	TAFAMIDIS MEGLUMINE	Tafamidis is becoming very competitive market especially for API supplier. There are more than 10 DMFs filed so far. As per FDA website 4 ANDAs were submitted on NCE-1 date for Tafamidis 61 MG capsule. NCE-1 date was in May 2023. Tafamidis is medication used to delay disease progression in adults with certain forms of transthyretin amyloidosis i.e., stiff heart syndrome.
AMI LIFESCIENCES PRIVATE LTD	DAPRODUSTAT	This is very quick DMF filing by Ami. Daprodustat was approved in February 2023. It must be very quick work by Ami Lifesciences and they must have started API development work much before FDA approval.  Daprodustat is approved to treat anaemia in people with chronic kidney failure
VIYASH LIFE SCIENCES PRIVATE LTD	BACLOFEN USP	Baclofen is used to relax certain muscles in body. There are 7 DMFs filed. According to IQVIA, and as per public domain information, U.S. annual sales for baclofen for the 12 months ended March 2022 were $130 million, but this could be only related to oral solid dosage forms.
AMOLI ORGANICS PRIVATE LTD	VARENICLINE TARTRATE	This will be very competitive API for US markets as a second source. There are already more than 16 DMFs. Varenicline Spray approval was in 2021 and it could have specific particle size requirement for the API. Varenicline tablets, 0.5 mg and 1 mg, had annual sales of $ 501 million (IQVIA MAT Mar 2023). This is low volume and high value API.
LEE PHARMA LTD	DAPAGLIFLOZIN	There are 40 DMFs. Generics must wait till October 2025 in US as per recent court decision. This is going to be very competitive market for API supplier. It will be interesting to find out which polymorph Lee Pharma had filed in their DMF, as polymorph will play very important role in dapagliflozin launch in October 2025.

General information

Mallinckrodt to Go Bankrupt for Second Time in Three Years

Mallinckrodt Plc plans to file bankruptcy for the second time in less than three years after battling business declines and struggling to keep up with payments on a $1.7 billion settlement resolving a wave of lawsuits accusing the drugmaker of fueling the US opioid epidemic

News here.

A novel approach to boost drug development in paediatric oncology

Despite major advances in cancer research, we are falling short in bringing innovative medicines to children with cancer. We propose a new business model to incentivize investors, private companies and public organizations to invest in drug development for paediatric cancers.

News here

Intellectual Property 

Delaware district court found Lonsurf patent valid and infringed.

Trifluridine/tipiracil (FTD–TPI), sold under the brand name Lonsurf, is a fixed-dose combination medication that is used as a third- or fourth-line treatment of metastatic colorectal cancer or gastric cancer, after chemotherapy and targeted therapeutics have failed.

USFDA approved Lonsurf in September 2015. It is called TAS-102 therapy.

As per IQVIA data, Lonsurf had generated annual sales of $211 million in USA during the twelve months ended in December 2022

Aurobindo, Accord, MSN Pharma, Natco (defendants) filed ANDAs with the FDA to market generic version. 

The innovator Taiho alleged that Defendants’ ANDA submissions constitute infringement U.S. Patent No. RE46,284. Other OB listed patents are as below.

Patent No	Patent Expiration	Drug Substance	Drug Product	Patent Use Code	Submission Date
9527833	06/17/2034	DS	DP		01/27/2017
9943537	09/05/2034			U-3659	08/07/2023
10456399	02/03/2037			U-3657 U-3658	11/08/2019
10457666	06/17/2034	DS	DP		11/08/2019
10960004	02/03/2037			U-3657 U-3658	04/09/2021
RE46284	09/22/2029			U-1751 U-2503 U-3656	02/07/2017

Independent claim 1 of the #284 patent reads: 

A method for treating at least one of a digestive cancer and a breast cancer, comprising orally administering a composition comprising a,a,a-trifluorothymidine {FTD) and 5-chloro-6-(1- (2-iminopyrrolidinyl)methyl)uracil hydrochloride in a molar ratio of 1 :0.5 at a dose of 50 to 70 mg/m2 /day in terms of FTD in 2 [or 3) divided portions per day to a human patient in need of treatment of at least one of a digestive cancer and a breast cancer, wherein the administration of a daily dose of said composition is in 2 [or 3) portions per day for 5 days followed by 2 days off treatment in the week on a one-week dosing schedule wherein m2 is the human patient's body surface area.

Claim 10 depends from claim 1 and reads: The method [ according to] of claim 1, wherein the [cancer] method is for treating digestive cancer which is selected from the group consisting of esophageal, gastric, liver, gallbladder-bile duct, pancreatic, and colorectal cancers.

Claim 13 depends from claim 10 and reads, "The method of claim 10, wherein the digestive cancer is colorectal cancer."

Defendants contend that they have proven by clear and convincing evidence that the RE46284 patent is invalid for obviousness. The Hon. Judge disagreed. He found that that every element of claims  except for twice-daily dosing is explicitly disclosed in the prior art. But he also found that twice-daily dosing is not explicitly disclosed in the art and that defendants did not adduce clear and convincing evidence that based on prior art documents discussed during proceedings, an artisan of ordinary skill would have been motivated to administer TAS-102 in two divided portions per day. 

Accordingly, the Judge concluded that defendants have not proven by clear and convincing evidence that claims of the `284 patent is invalid for obviousness.

Decision here.