U.S. International Trade Commission Covid-19 Diagnostics and Treatment Development and Access Report

The U.S. International Trade Commission released a corrected version of its COVID-19 Diagnostics and Therapeutics: Supply, Demand and TRIPS Flexibilities Report in December of 2023.  Chapter 7 is a summary of views of interested parties.  I found that interesting, particularly the section on jobs related to the pharmaceutical and biotech industries.  The following is an excerpt from the Executive Summary:

The TRIPS Agreement sets minimum standards for the protection and enforcement of IP rights. It also includes flexibilities. Persons providing input to the Commission disagreed about the extent to which the 2022 Ministerial Decision expands flexibilities and whether the decision should be extended to COVID-19 diagnostics and therapeutics.

Determining a definitive scope of what products are covered by the terms “diagnostics” and “therapeutics” as they pertain to COVID-19 and what constitutes relevant COVID-19 diagnostics and therapeutics covered by patents is complicated and subject to interpretation. Based on definitions in the medical field of “diagnostics” and “therapeutics,” a COVID-19 diagnostic is a good used to diagnose or identify how patients respond to treatments for COVID-19, and a COVID-19 therapeutic is a good used to treat COVID-19. The universe of COVID-19 diagnostics and therapeutics covered by patents or in development that fall within those definitions is broad and varied. There are various parameters that could be applied, individually or in combination, to identify relevant COVID-19 diagnostics and therapeutics, including whether the product is covered by patent, whether the product is directed to COVID-19 (virus-directed), and whether the product has received regulatory approval or authorization; application of each comes with its own challenges.

The development and commercialization of COVID-19 diagnostics and therapeutics occurred on an extremely compressed timeline. Manufacturing of diagnostics and therapeutics involves multiple stages, each of which requires careful attention to detail and strict quality control measures. The two fields of diagnostics and therapeutics are composed of different producers, inputs, know-how, and so on. Generally, COVID-19 diagnostics can be brought to market faster than COVID-19 therapeutics, and the knowledge and manufacturing base globally for small-molecule drugs is larger than for biologics. Research and development of virus-directed COVID-19 diagnostics and therapeutics primarily occurred in HICs, but manufacturing of diagnostics and therapeutics occurred in countries of all income levels except for LICs. As of summer 2023, China (UMIC) reportedly had the highest number of manufacturers of COVID-19 diagnostics (247), and India (LMIC) had the largest number of reported therapeutics manufacturers (56). It is difficult, however, to ascertain how much COVID-19 diagnostics and therapeutics production came online or is still ongoing.

A variety of advantages and challenges are associated with the use of voluntary licenses to provide access to IP associated with COVID-19 therapeutics and compulsory licenses to access COVID-19 therapeutics and other patented pharmaceutical products. Voluntary licenses and compulsory licenses generally were not used to access IP associated with COVID-19 diagnostics. Voluntary licenses have been an important mechanism that was used to offer COVID-19 therapeutics for sale at reduced prices in LICs, LMICs, and some UMICs; however, many UMICs have been excluded from coverage under voluntary licenses. Voluntary licenses also provided a mechanism for technology transfer and knowledge sharing to support the manufacture and regulatory approval of less expensive licensed products. Compulsory licenses have been used by a small number of countries to access IP associated with certain COVID-19 therapeutics. The primary, commonly cited benefits for countries utilizing compulsory licenses are reduced costs and improved access. Another primary benefit of compulsory licenses reportedly is that they provide leverage to negotiate voluntary licenses. One of the main disadvantages is that they do not provide a basis for sharing knowledge.

The availability of supplies to meet global demand for COVID-19 diagnostics and therapeutics has been a moving target throughout the pandemic. Estimates or calculations of demand for these goods differ depending upon whether the metric is market demand or need. When infection rates rose sharply in early 2021, before manufacturers had scaled up production and regulators had granted approvals, access was limited and available only to a few HICs. During 2021, more products became available for procurement. By early 2022, infection rates and deaths from COVID-19 steadily declined as vaccination rates grew and natural immunity strengthened. By early May 2023, the World Health Organization (WHO) declared that COVID-19 would no longer be classified as a public health emergency of international concern. Today, market demand has waned in some countries, with several manufacturers no longer pursuing regulatory approval and stopping production altogether.

The disparity among countries of different income groups is wide in terms of access and availability to COVID-19 diagnostics and therapeutics. About 80 percent of government procurements were by HICs, 14 percent by UMICs, and 5 percent by LMICs. No government purchases were made by LICs, although products were made available to them through multilateral organizations. The wide disparity among countries in their ability to access COVID-19 diagnostics and therapeutics is the result of multiple factors, including access to IP, prices and affordability, regulatory approvals, healthcare infrastructure, and the healthcare priorities of governments. The importance of each of these and other factors impacting availability and demand varies greatly among countries, although high prices and the lack of price transparency appear detrimental to many countries seeking access.

Academic literature on the effects of patent protection, compulsory licenses, and the MPP is limited and would benefit from additional research. From the available evidence, patent protection is generally found to be more beneficial to innovation in the health sector for developed countries and less so for developing countries. Patent protection is often found to result in higher prices for medicines, which decrease access, but patent protection can also have some counteracting effects, such as increases in international trade flows of pharmaceuticals and faster drug launches in markets, that help improve access. Researchers have found that compulsory licenses and the MPP are associated with increased generics and lower prices, and increased access to pharmaceuticals. Researchers have not studied the relationship between compulsory licenses and the MPP and access to COVID-19 diagnostics and therapeutics.

University of Michigan Spin-off Company Develops Covid-19 Test

A University of Michigan spin-off company has developed a promising Covid-19 antibody test.  The press release states: 

ANN ARBOR—COVID-19 antibody testing that’s portable, fast, cheap and highly precise—four attributes that are usually mutually exclusive—could be possible with a microfluidic device invented at the University of Michigan and developed by U-M startup Optofluidic Bioassay.

A microfluidic device, or “lab on a chip,” shrinks multiple lab functions onto a single chip just millimeters or centimeters in size. The technology enables faster results with smaller sample sizes.

The new system is believed to be the first microfluidic approach to a gold standard testing protocol known as “enzyme-linked immunosorbent assay,” or ELISA. The U-M researchers have previously published results showing that their device can work as well as the slower, larger, standard ELISA setup. They are currently validating it for use on COVID-19 antibodies.

They have demonstrated that they can detect synthetic COVID-19 antibodies and they’re working with researchers at a hospital in New Jersey on experiments with human blood from COVID-19 patients.

University and industry labs around the U.S. are clambering to develop better antibody tests. The U-M approach is different in that it centers on a device, rather than the chemical mixtures, or reagents, to detect COVID-19 markers.

“We are unique because we are a hardware company,” said Xudong (Sherman) Fan, U-M biomedical engineering professor and co-founder of Optofluidic Bioassay. “Anyone working on COVID-19 antibody tests can use their reagents in our device.”

Why we need antibody tests

Rapid and accurate antibody tests could play an important role as governments, medical workers, scientists and private citizens alike continue to navigate the pandemic, the researchers say. Antibody tests can reveal who has already been exposed to the virus and developed immunity, at least temporarily, and can safely go back to work. If done in a widespread way, they could show the true scale of the pandemic and its death rate.

And the U-M researchers say their particular approach could give doctors critical, near-real-time insights into how a patient is responding to treatment, or a vaccine once one is developed.

Small-scale antibody testing has been done in some countries. Research projects are underway in the U.S. and while kits are beginning to materialize on the market here, they’re not yet widely available.

Antibody, or “serology” tests are different from the “PCR” tests being used to diagnose COVID-19. Rather than screen for the virus itself, serology tests detect antibodies—proteins the immune system manufactures to fight it.

Microfluidic ELISA in the landscape of COVID-19 antibody tests

The majority of labs working on serology kits are making a particular type called “rapid diagnostic tests” that give a yes or no reading. These are quick, but they have drawbacks. False positives can be a problem. And because they don’t give a lot of information, they aren’t useful in monitoring the immune system’s response during treatment.

A handful of labs are making ELISA tests. These are typically quantitative and accurate, showing the concentration of antibodies. That makes them more reliable and less prone to false positives than the rapid diagnostic tests. But standard ELISA results take several hours, and the machines that provide them are the size of refrigerators. In addition, the sample needs to be sent to the test lab for analysis.

But microfluidic ELISA can give a quantitative and accurate result in just 15 minutes, with a finger-prick’s worth of blood. This combination of attributes, plus the fact that it’s portable, could make it a powerful tool.

“Our approach offers the best of both worlds. We can achieve the quickness and simplicity of the rapid diagnostic test with the accuracy of the standard ELISA quantitative measure,” Fan said.

“Because our device generates such sensitive and quantitative measurements, we believe its use goes beyond identifying recovered patients. Antibodies begin to show up a few days after infection, so we could use this approach to monitor patients’ immune response to infection, treatment and vaccination.”

The microfluidic ELISA is rapid, portable and low cost.

“The estimated cost of testing is a few dollars per test of two to three different antibodies, making this a very viable option for use in hospitals, doctors’ offices, field clinics and potentially even pharmacies,” said Xiaotian Tan, a doctoral student in biomedical engineering who is working on COVID-19 antibody testing with Fan.

The machine can be the size of a microwave, and can test multiple simultaneous samples of little more than a drop of blood from a fingertip in less than 20 minutes.

It was invented at U-M several years ago and developed by Optofluidic Bioassay, which was founded by Fan and former research investigator of biomedical engineering, Maung (Malcolm) Khaing Oo, who now serves as the company’’ chief technology officer. Fan and Maung Khaing Oo are co-founders of and have an equity interest in Optofluidic Bioassay. The researchers plan to eventually apply for FDA Emergency Use Authorization.

Intellectual Property Owners Association Adopts Resolution to Amend Patent Eligible Subject Matter

The Intellectual Property Owners Association (IPO) board of directors has adopted a resolution which advocates for amending section 101 of the Patent Act in the U.S. to essentially overturn Mayo v. Prometheus and Alice v. CLS Bank.  The reason for the resolution is the development of inconsistent application of the so-called Alice/Mayo test.  Indeed, there have been a number of relatively recent decisions attempting to clarify Alice/Mayo which find patent eligible subject matter satisfied, including DDR, Enfish, McRO, Amdocs, and Cellz Direct.  How does this happen: the development of panel splits at the U.S. Court of Appeals for the Federal Circuit.  Notably, the United States Patent and Trademark Office (USPTO) has worked extremely hard in attempting to provide guidance to patentees and arguably is doing quite a good job.  I think the USPTO deserves a lot of credit for attempting to bring clarity and predictability to the field.  My personal opinion (shared by others) is that section 102 and 103 could provide a better gatekeeper than section 101 even though early resolution may be difficult.  I do think that the USPTO’s attempt to place certain claims in a “streamlined” analysis seems to be a good idea.  Claims drafting gamesmanship and looking at the claim as a whole will always raise issues though (that pesky Diamond v. Diehr!).  Here is the proposed language amending section 101:

101(a) ELIGIBLE SUBJECT MATTER
Whoever invents or discovers, and claims as an invention, any useful process, machine, manufacture, composition of matter, or any useful improvement thereto, shall be entitled to a patent for a claimed invention thereof, subject only to the exceptions, conditions, and requirements set forth in this Title.

101(b) SOLE EXCEPTION TO SUBJECT MATTER ELIGIBILITY
A claimed invention is ineligible under subsection (a) if and only if the claimed invention as a whole, as understood by a person having ordinary skill in the art to which the claimed invention pertains, exists in nature independently of and prior to any human activity, or exists solely in the human mind.

101(c) SOLE ELIGIBILITY STANDARD
The eligibility of a claimed invention under subsections (a) and (b) shall be determined without regard as to the requirements or conditions of sections 102, 103, and 112 of this Title, the manner in which the claimed invention was made or discovered, or the claimed invention’s inventive concept.