API and IP Newsletter
Contents
Analysis of imports of Biophore.
General information.
Aspen Gets Unsolicited Offers for Pharma Ingredient Unit
Facilitating production of APIs.
Intellectual Property.
Inequitable conduct
Analysis of imports of Biophore
In our firm we analyze development portfolios of many companies based on public domain information such as patent application filings and import-export database etc. This week we chose Biophore. As per their website information, they have filed over 60 DMFs so far.
So, analyzing their imports we tried to understand their development portfolio, the probable stage of their development etc. The glimpse of our analysis is published here.
General information
Aspen Gets Unsolicited Offers for Pharma Ingredient Unit
Aspen Pharmacare Holdings Ltd. has received two unsolicited offers for its active pharmaceutical ingredient business and will start a process aimed at evaluating proposals for the unit.
The disposal of an infant-formula business to Lactalis International and a Japanese unit to Novartis AG in 2019 helped the drugmaker reduce borrowings, as did the agreed sale of its European thrombosis division to U.S. drugmaker Mylan NV in 2020.
News here.
Facilitating production of APIs
The recent decision taken by the National Board of Revenue (NBR) to extend tax holiday facility to pharmaceutical firms manufacturing active pharmaceutical ingredients (APIs) and laboratory regents is indeed an important move. According to industry insiders, this waiver --- a well targeted move as well as a much sought-after fiscal incentive --- will have a very positive impact on the manufacture of some of the most vital pharma ingredients towards meeting both local and overseas demands.
News here.
Intellectual Property
Inequitable conduct
Belcher sued Hospira for infringement of a patent covering formulation of l-epinephrine having a pH between 2.8 and 3.3. Matter was before CAFC. On 01 September 2021 CAFC affirmed the Delaware district court’s decision of patent unenforceable for inequitable conduct.
OB listed patents are as below. This litigation is about US 9283197 (`197)
What is claimed briefly in `197 :
1. A liquid pharmaceutical formulation of preservative-free and sulfite-free, 1 mg per mL l-epinephrine sterile solution for uses including injection; said liquid pharmaceutical formulation having a pH between 2.8 and 3.3;---
The essential element of the claim was pH. It was told to the patent office during prosecution that with this pH there is an unexpected result. The examiner granted the patent.
Belcher’s Chief Science Officer (CSO), Mr. Darren Rubin, was involved in prosecution of the patent as well as regulatory approval from the FDA.
Story goes like this
1. On 30 November 2012, Belcher Pharmaceuticals, LLC (Belcher) submitted NDA for a 1 mg/mL injectable l-epinephrine formulation.
2. The NDA was literature-based, meaning that Belcher did not perform any clinical or nonclinical studies on its epinephrine formulation to support its application.
3. The NDA described the development of Belcher’s formulation, it first discussed Swiss company Sintetica SA’s (“Sintetica”) “original formulation” of 1 mg/mL injectable l-epinephrine, which Sintetica developed in the 1930s and registered in Switzerland in 1947. The formulation included sodium metabisulphite as an antioxidant preservative and about a 10 percent overage of epinephrine to ward off activity loss, and it had a pH range of 2.2 to 4.0.
4. The manufacturing process involved a continuous flow of nitrogen gas to remove oxygen and thereby enhance stability.
5. In the 2000s, in US market demand shifted to epinephrine formulations that did not include “preservatives and sulfites,” which had been found to cause side effects. Belcher grabbed the opportunity.
6. Their NDA described the new composition as having a pH range of 2.8 to 3.3.
7. Given the removal of the sulfite antioxidant, “careful attention was paid to the nitrogen purge during the whole process” to maximize stability in the absence of the antioxidant.
8. On 07 February 2013, FDA sent a letter to Belcher asking for certain additional information, including (i) “data that support evaluation of the drug product for potential racemization from manufacturing process conditions and over the shelf life,” and (ii) clarification on whether the Sintetica batches on which Belcher relied for stability validation were manufactured in the same way as that proposed for marketing.
9. Belcher forwarded the letter to Sintetica asking for assistance in responding to the FDA’s requests.
10. On 04 October 2013, FDA further asked Belcher to evaluate the effect of an in-process pH range of 2.4 to 2.6 on racemization.
11. On 17 October 2013, Belcher’s regulatory consultants, INC Research, recommended that Belcher revert to the 2.8 to 3.3 pH range (as an in-process pH range) shown in the Sintetica batch data because deviating from that range would delay the FDA’s approval. All this correspondence was between FDA and Belcher.
12. On another front, Jugal Taneja, Belcher’s CEO, filed U.S. Patent Application which issued as US 9,283,197 (“the ’197 patent”). Mr. Taneja later assigned the application to Belcher. It was a tough prosecution.
13. On 16 December 2015, after holding an interview, the patent examiner withdrew the pending rejections, made an examiner’s amendment approved by the applicant, and allowed the patent.
14. In discussing the reasons for allowance, the examiner explained that the cited art failed to render the claims unpatentable “in view of Applicant’s demonstration of criticality of a pH range between 2.8 and 3.3.
15. According to the examiner, Applicant has demonstrated that pH range of between 2.8 and 3.3 is critical to prevent racemization of l-epinephrine . Finally, the ’197 patent was issued on 15 March 2016, and the FDA thereafter listed the ’197 patent on 07 April 2016.
16. Hospira submitted a dossier to the FDA seeking approval of a 0.1 mg/mL injectable l-epinephrine formulation and provided P-IV certification to US’197 patent.
17. On 16 June 2017, Belcher sued Hospira for infringement of `197.
18. One of the trial witnesses was Mr. Darren Rubin, Belcher’s CSO. Mr. Rubin testified that he was a consultant for Belcher from 2010 to 2014 and became its CSO in 2015.
19. He holds degrees in biology, medical sciences, and business but is neither a registered patent agent nor an attorney.
20. Within Belcher, Mr. Rubin was referred to as the head of intellectual property.
21. His job responsibilities included overseeing regulatory approvals, product development, and working on intellectual property matters including patent application drafting, prosecution, and litigation.
22. Mr. Rubin explained that he was involved in the development of Belcher’s NDA product and participated in drafting the NDA.
23. Mr. Rubin also testified that he was involved in the prosecution of the ’197 patent. He helped draft the application, including its claims and specification, and helped respond to the examiner’s office action. In fact, he served as liaison between inventor Mr. Taneja, Belcher’s patent prosecution attorney, and the USPTO
24. Mr. Rubin testified that he possessed knowledge of certain facts pertinent to this appeal before and during the ’197 patent’s prosecution. For example, he knew of Sintetica’s epinephrine formulations that had a pH range of 2.8 to 3.3 and that Belcher’s NDA described that range as “old.”
25. Mr. Rubin also admitted that, by October 2013, he possessed a label for a 1 mg/mL epinephrine product that a company named JHP had already introduced to the market.
26. JHP’s label described its epinephrine product as having a pH in the range of 2.2 to 5.0.. Belcher also acquired three batches of the JHP product and sent them to Sintetica for testing, which showed that the JHP product had a pH within the range of 2.8 to 3.3 (specifically 2.9, 2.9, and 3.1) at 15 months, i.e., three months before the expiration of its 18- month shelf life.
After understanding all facts on 31 March 2020, the district court decided, among other things, that the ’197 patent is unenforceable for inequitable conduct. On 02 September 2021 CAFC confirmed the district court’s decision.
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.
