API and IP Newsletter
Contents
The drug, 2-deoxy-D-glucose (2DG)
General information.
KemPharm, Inc. Announces Orange Book Listing for Six Patents Covering Serdexmethylphenidate (SDX) and Confirmation of NCE Status.
A patent waiver on COVID vaccines is right and fair
Intellectual Property.
Enalapril Maleate Solution Oral Solution.
The drug, 2-deoxy-D-glucose (2DG)
The Drugs Controller General of India (DCGI) approved a drug 2-deoxy-D-glucose (2-DG) developed by the DRDO for the treatment of Covid 19, as an adjuvant therapy.
Lot of discussions about mechanism of the drug in the public domain by now. Everybody knows, it is an analogue of D-Glucose, the hydroxyl group at the second position carbon of D-Glucose is replaced by a hydrogen, the drug works as an anticancer and antiviral by inhibiting proliferating cells of nutrition. There are articles which explain how the drug inhibits glucose metabolism and protein glycosylation.
We will stick to API synthesis.
It is reported in US6933382B2 in example 12.
A mixture of methyl 2-deoxy-α/β-D-glucopyranoside (24 g) (synthesis in the same patent as an example 2) water (125 ml) and IR 120H+ resin (7.5 ml) was heated to 90-95° C. for 2 hours. The reaction mixture was cooled to room temperature, filtered and the resin was washed with water (20 ml). The filtrate was concentrated to residue and crystallized from ethanol to obtain 2-deoxy-D-glucose (8.8 g), mp. 150-152° C.
According to the patentee, following are the advantages over the prior art.
1. It does not involve the use of toxic mercaptans like ethane thiol.
2. This process does not involve reaction of D-glucal with mineral acid, thereby avoiding the formation of Ferrier by-products.
This patent application filed by Council of Scientific and Industrial Research, New Delhi (in December 2002. Legal Status to be checked.
General information
KemPharm, Inc. Announces Orange Book Listing for Six Patents Covering Serdexmethylphenidate (SDX) and Confirmation of NCE Status
KemPharm, Inc. (NASDAQ: KMPH), a specialty pharmaceutical company focused on the discovery and development of proprietary prodrugs, today announced that six U.S. patents governing Serdexmethylphenidate are listed in OB. News here.
A patent waiver on COVID vaccines is right and fair
The core problem is that vaccine manufacturing, research and development is too heavily concentrated in a small group of high- and middle-income countries. Companies in these countries, which are also the main IP holders, have sold most of the available vaccine doses to their own governments, and to governments of other high-income nations. Some 6 billion doses out of the 8.6 billion confirmed purchases so far have been pre-ordered by governments in high and middle-income countries.(Read more)
Intellectual Property
Enalapril Maleate Solution Oral Solution
Enalapril maleate 1 MG/ML oral solution (Epaned) was approved in 2016 for treatment of hypertension in adults and children older than 1 month, to lower the blood pressure.
Innovator: Silvergate
ANDA filer: Bionpharma
Below are the patents listed in OB.
Litigation was mainly about two patents, US 10,039,745, and US 10,154,987
The relevant part of the Claims for our discussion are as follows:
US 10039745
A stable oral liquid formulation, comprising:
(i) about 0.6 to about 1.2 mg/ml enalapril or a pharmaceutically acceptable salt or solvate thereof;
(ii) a buffer comprising about 0.8 to about 3.5 mg/ml citric acid and about 0.1 to about 0.8 mg/ml sodium citrate;
(iii) about 0.7 to about 1.2 mg/ml sodium benzoate; and
(iv) water; _______ ____
US 1015987
A method of treating hypertension ---- the stable oral liquid formulation comprising:
(i) about 0.6 to about 1.2 mg/ml enalapril or a pharmaceutically acceptable salt or solvate thereof;
(ii) a buffer comprising about 0.8 to about 3.5 mg/ml citric acid and about 0.1 to about 0.8 mg/ml sodium citrate;
(iii) about 0.7 to about 1.2 mg/ml sodium benzoate; and
(iv) water; _____ ____
Silvergate argued doctrine of equivalence (DoE). Stated, Bionpharma does not directly infringe these patents but these patents are infringed under DoE.
It is interesting to note, during the patent prosecution, Silvergate submitted that the specific concentration of citric acid and sodium citrate is distinguishing the invention from the prior art. Hence, Silvegate amended claims to include limitation of 0.1 to about 0.8 mg/ml sodium citrate in the claim. It was also stated during the prosecution that these buffers are critical to the stability of the solution.
When an inventor makes narrowing amendments to the claims of the application to seek grant of the patent, he may be precluded from invoking the doctrine of equivalents (DoE) at the later date. This is called prosecution history estopel.
Please note, in below paragraph in formulation patent prosecution in the same family what was stated by Silvergate.
Based on this Court further said, Silvergate disclaimed all formulations not containing both 1.82 mg/mL of citric acid and 0.15 mg/mL of sodium citrate dihydrate.
Moreover, Bionpharma ANDA was devoid of sodium benzoate.
Court opined in favor of Bionpharma.
News here.
Disclaimer
Sidvim LifeSciences Private Ltd has taken due care and caution in developing this document. Since the data used for analysis in this document is based on the information available in the public domain, its adequacy or accuracy or completeness cannot be guaranteed. This document is for information only and Sidvim is not responsible for losses that may or may not arise due to any decisions made based on the same. No part of the document shall constitute or be represented as a legal opinion of any kind or nature. No warranties or guarantees, expressed or implied, are included in or intended by the document, except that it has been prepared in accordance with the current generally accepted practices and standards consistent with the level of care and skill exercised under similar circumstances by professional consultants or firms that perform the same or similar services.
