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PTAB decision highlights the value of a robust IP portfolio

PTAB decision highlights the value of a robust IP portfolio

Industry news 10/09/2020

A recent decision by the US Patent Trial & Appeal Board (PTAB) has highlighted the benefits of a strong intellectual property portfolio, particularly in relation to smaller biotech companies.

A US Biotech Company, Moderna, has been in the news regularly since the outbreak of the novel coronavirus pandemic. Moderna are developers of mRNA vaccines and are one of the front runners in the race for a SARS-CoV-2 vaccine.

On 23 July 2020, Moderna was on the losing side of a decision by the US Patent Trial and Appeal Board (PTAB).

That decision relates to a US patent owned by the Canadian biotech company Arbutus Biopharma. Moderna initiated a review of certain claims in Arbutus’ U.S. Patent No. 8,058,069 B2 (“the ’069 patent”).

The ‘069 patent relates to lipid formulations for nucleic acid delivery and, in particular, “stable nucleic acid-lipid particles”. These nucleic-acid lipid particles may be used to deliver nucleic acids to cells for therapeutic purposes such as RNA interference. Nucleic acid lipid particles are known to be vital to much of Moderna’s vaccine technology, including their nascent COVID-19 vaccine – ‘mRNA-1273’.

In the published decision, the PTAB concluded that Moderna failed to demonstrate that the claims lacked novelty or inventiveness. Thus, the court rejected Moderna’s arguments and maintained the ‘069 patent.

In response to the decision, Moderna released a press statement on 24 July 2020 in which it stated it was not aware of any “significant intellectual property impediments” to its COVID-19 vaccine. In addition, Moderna has stated that their technology has advanced beyond Arbutus’ patented products.

The ‘069 patent claims a nucleic acid-lipid particle comprising (a) a nucleic acid; (b) a cationic lipid in a specified concentration; (c) a non-cationic lipid comprising a mixture of a phospholipid and cholesterol or a derivative thereof, each in specified molar ratios; and (d) a conjugated lipid that inhibits aggregation of particles again in a specified molar ratios.

On the face of it, to infringe the 069’patent, a product must comprise the following components; (i) a nucleic acid; (ii) cationic lipid; (iii) phospholipid; (iv) cholesterol (or a derivative thereof); and (v) conjugated lipid. Furthermore, where the lipid components are concerned, they should be present in the recited molar ratios.

A publication of a preclinical study wherein Moderna’s “mRNA-1273” vaccine was tested in mice disclosed that the vaccine comprises a self-replicating mRNA - encoding the 2019nCoV spike protein - encapsulated within a lipid nanoparticle at a molar ratio of 50:10:38.5:1.5 (ionizable lipid:DSPC:cholesterol:PEG-lipid).

Thus, mRNA-1273 of the publication appears to include at least several, and possibly all, of the components recited in claim 1 of the ‘069 patent. Firstly, mRNA-1273 contains a nucleic acid payload encoding the pre fusion stabilized spike protein of 2019nCoV. Secondly, the vaccine utilizes an “ionizable lipid” at 50% total lipid content. However, exactly whether this lipid is ‘cationic’ is unclear. Thirdly, mRNA-1273 contains a non-cationic lipid mixture comprising a phospholipid (DSPC) and cholesterol at molar ratios of 10% and 38.5%, respectively. And finally, the vaccine comprises an aggregate inhibiting conjugated lipid (PEG-lipid), present at a molar ratio of 1.5%.

Interestingly, a peer-reviewed preclinical study testing Moderna’s mRNA-1273 vaccine in non-human primates was published in the NEMJ on Tuesday 28 July 2020. Therein it is disclosed that mRNA-1273 is formulated as described in a previous publication authored by Moderna Scientists -Hasset et al, Molecular Therapy Nucleic Acids, 2019.

The publication indicates that the lipid nanoparticles are formulated in an identical ratio to that described in the preclinical mouse study (50:10:38.5:1.5 - ionizable lipid: DSPC:cholesterol:PEG-lipid). It is further disclosed that the ionizable lipid components of the nanoparticles are composed of proprietary ionizable lipids owned by Moderna. Indeed, registration of Moderna’s Phase I trial in humans with the US National Institute for Health shows that the mRNA-1273 vaccine comprises a lipid nanoparticle formulation comprised of a proprietary ionizable lipid, termed SM-102. The exact structure of SM-102 is not disclosed and it is unknown whether SM-102 carries a net positive charge at physiological pH, as recited in the ‘069 patent.

Furthermore, it is noted that Moderna has stated that the vaccine used in these publications is not necessarily the product going through clinical trials for the prevention of COVID-19.

Interestingly, however, on 6 August 2020, Moderna released their SEC filing which disclosed their quarterly report providing a view of the company’s financial situation. The report included the following statements:

“There are many issued and pending third-party patents that claim aspects of oligonucleotide delivery technologies that we may need for our mRNA therapeutic and vaccine candidates or marketed products, including mRNA-1273, if approved.

In addition, there may be issued and pending patent applications that may be asserted against us in a court proceeding or otherwise based upon the asserting party’s belief that we may need such patents for our mRNA therapeutic candidates. Thus, it is possible that one or more organizations will hold patent rights to which we may need a license, or hold patent rights which could be asserted against us. If those organizations refuse to grant us a license to such patent rights on reasonable terms or a court rules that we need such patent rights that have been asserted against us and we are not able to obtain a license on reasonable terms, we may be unable to perform research and development or other activities or market products, including mRNA-1273, covered by such patents.”

It is not clear whether Moderna’s statement is referring to the ‘069 patent. However, it is apparent that the field of oligonucleotide delivery systems is a crowded one and without assignment and/or licence, Moderna may not yet possess freedom to operate their mRNA products, including mRNA-1273.

Lipid nanoparticle drug formulations are growing in importance and prevalence, particularly in the fields of gene therapy and vaccine technology. Indeed, mRNA-1273 is not the only product utilizing a lipid nanoparticle formulation within a COVID-19 vaccine. BioNTech, which is partnered with American drug giant Pfizer, have sublicensed the lipid nanoparticle technology covered by ‘069 for use in one of their potential COVID-19 vaccine - BNT162 mRNA. Interestingly, BioNTech may already have access to the Arbutus patent portfolio via an agreement between BioNTech and Genevant, a venture founded by Arbutus and Riovant Sciences.

If nothing else, however, the Moderna-Arbutus dispute highlights many of the benefits provided by a strong intellectual property portfolio, particularly in the context of smaller biotech companies which may have few or no tangible products on the market. Indeed, licensing patented technologies, like the lipid nanoparticle technology of the ‘069 patent, can be extremely lucrative for smaller companies looking to maintain a competitive edge by developing industry-leading methods. Whether this may ultimately be the case in this instance remains to be seen.