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Monday, April 22, 2024

Supreme Court rejects Vanda Pharmaceuticals case over sleep-drug patents

 The U.S. Supreme Court on Monday declined to hear a bid by Vanda Pharmaceuticals to revive patents for its sleep-disorder drug Hetlioz that were previously declared invalid in a dispute with generic drugmakers Teva and Apotex.

The justices turned away Vanda's appeal of a ruling by the patent-focused U.S. Court of Appeals for the Federal Circuit against the company, which in 2018 had sued Teva and Apotex in Delaware for patent infringement after they applied to make generic versions of Vanda's Hetlioz, a circadian-rhythm drug used to treat rare sleep disorders.

In the case, the Supreme Court declined a chance to consider for the first time since 2007 when a patent can be invalidated as "obvious" based on earlier publications describing the same invention.

"The Federal Circuit's obviousness standard materially departs from the Supreme Court's longstanding holdings," Vanda attorney Paul Hughes said. "While we are disappointed that the Supreme Court declined review of this case, we remain hopeful that the court will ultimately correct the governing standard."

"Doing so is imperative in the pharmaceutical context, to ensure that life-changing therapeutics are timely developed and reach underserved patients," Hughes added.

A Teva spokesperson said that the company was pleased with the Supreme Court's action. Representatives for Apotex did not immediately respond to a request for comment.

Washington-based Vanda earned more than $100 million from sales of Hetlioz in 2023, according to a company report.

U.S. District Judge Colm Connolly ruled against Vanda and cleared a hurdle for the generics in 2022. Connolly found Vanda's patents invalid based on clinical trial results, U.S. Food and Drug Administration guidance and other documents that, when combined, would have made the patented inventions obvious to a scientist in the field.

The Federal Circuit upheld the decision in 2023. Vanda asked the Supreme Court in January to hear its appeal.

Vanda told the justices that the Federal Circuit has "charted its own course" and adopted a lower standard than the Supreme Court mandated for determining obviousness.

"Most relevant here, it threatens to render many advancements in drug development unpatentable," Vanda said. "That is an especially pernicious result for rare diseases, where patent-based incentives are crucial for innovators to invest the billions required to develop new, successful treatments."

REPO Act Passage Has Authorized Biden To Confiscate Russian Assets & Transfer To Ukraine

 When the House voted to pass Biden's long sought after foreign aid package Saturday, which will deliver over $60 billion to Ukraine, included in this was passage of the REPO Act, which paves the way for the Biden administration confiscate billions in Russian sovereign assets which sit in US banks.

The US administration has been pursuing a controversial plan to transfer frozen Russian assets to Ukraine for reconstruction, and has been aggressively lobbying G7 countries to jump on board, also given most of the $300 billion in Russian assets are held in Europe - particularly France, Germany, and Belgium.

A summary of the REPO Act - H.R.4175 - on the Congressional website, reads: "This bill requires or authorizes various actions related to the confiscation and disposition of Russian sovereign assets (which include funds and other property of Russia's central bank, direct investment fund, or ministry of finance)."

"Under the bill, the President must require U.S. financial institutions to notify the Department of the Treasury of any Russian sovereign assets located at such institutions. The President may confiscate any such assets subject to U.S. jurisdiction," it continues. "Confiscated funds and the proceeds of liquidated property must be deposited into the Ukraine Support Fund established by the bill."

The now approved bill further specifies:

The Ukraine Support Fund shall be used by the Department of State to compensate Ukraine for damages caused by the Russian invasion. The Ukraine Support Fund may also support an international body or mechanism for (1) reconstruction and rebuilding efforts in Ukraine, (2) humanitarian assistance to the Ukrainian people, or (3) other purposes which support the recovery of Ukraine and the welfare of the Ukrainian people.

Importantly, it seeks to bring in international partners toward establishing a mechanism which would tap Russian assets in Europe. "The bill also directs the President to seek to establish, with foreign partners, an international mechanism to provide compensation to Ukraine using the Ukraine Support Fund and Russian sovereign assets confiscated by foreign partners," the legislation summary says.

But some EU leaders have expressed anxiety over the plan and have thus far resisted, mainly on concerns that it would undermine global trust and confidence in Western banks. Moscow could also see what it deems theft of its sovereign funds as essentially an act of war.

On Monday, the Kremlin reacted to the weekend passage of the REPO Act, vowing to fight and inflict corresponding punishment on the US and West. Putin Spokesman Dmitry Peskov told reporters:

"We are very skeptical about this, because this is essentially the destruction of all the foundations of the economic system. This is an encroachment on state property, on state assets and on private property. By no means should this be perceived as legal action - it is illegal. And accordingly, it will be subject to retaliatory actions and legal proceedings," the Kremlin official said.

"If such measures are implemented, of course, many investors will think ten times before making any investments in the American economy or storing their assets there," Peskov added, noting there's still a long, complex road ahead if Washington ultimately seeks to pull the trigger on stealing Russia's assets. "This is a very dangerous precedent," Peskov underscored.

Below: an interesting take from Sen. J.D. Vance...

Starting in February, US Treasury Secretary Janet Yellen began getting more vocal on the "moral case" for using Russian assets to aid Ukraine, telling allies they must find a way to "unlock the value" of the hundreds of billions in immobilized Russian assets, also with an eye towards Ukraine's post-war reconstruction.

Previously some Ukrainian officials floated the idea of "reparation bonds" backed by future claims for war damages against Moscow, and utilizing frozen Russian assets. These initiatives have gained steam under US leadership.

https://www.zerohedge.com/geopolitical/repo-act-passage-has-authorized-biden-confiscate-russian-assets-give-them-ukraine

'China freezes out Covid origins probe'

 The hunt for the origins of COVID-19 has gone dark in China, the victim of political infighting after a series of stalled and thwarted attempts to find the source of the virus that killed millions and paralyzed the world 

opens in a new tab or windowfor months.

The Chinese government frozeopens in a new tab or window meaningful domestic and international efforts to trace the virus from the first weeks of the outbreak, despite statements supporting open scientific inquiry, an Associated Press investigation found. That pattern continues to this day, with labs closed, collaborations shattered, foreign scientists forced out, and Chinese researchers barred from leaving the country.

The investigation drew on thousands of pages of undisclosed emails and documents and dozens of interviews that showed the freeze began far earlier than previously known and involved political and scientific infighting in China as much as international finger-pointing.

As early as Jan. 6, 2020, health officials in Beijing closed the lab of a Chinese scientist who sequenced the virus and barred researchers from working with him.

Scientists warn that willful blindness over the origins of the coronavirus leaves the world vulnerable to another outbreak, potentially undermining pandemic treaty talksopens in a new tab or window coordinated by the World Health Organizationopens in a new tab or window (WHO) set to culminate in May.

At the heart of the question is whether the virus jumped from an animal or came from a laboratory accident. A U.S. intelligence analysisopens in a new tab or window says there is insufficient evidence to prove either theory, but the debate has further tainted relations between the U.S. and China.

Unlike in the U.S., there is virtually no public debate in China about whether the virus came from nature or from a lab leak. In fact, there is little public discussion at all about the source of the disease, first detected in the central city of Wuhan.

Crucial initial efforts were hampered by bureaucrats in Wuhan trying to avoid blame who misled the central government; the central government, which muzzled Chinese scientists and subjected visiting WHO officials to stage-managed tours; and the U.N. health agency itself, which may have compromisedopens in a new tab or window early opportunities to gather critical information in hopes that by placating China, scientists could gain more access, according to internal materials obtained by the AP.

In a faxed statement, China's Foreign Ministry defended China's handling of research into the origins, saying the country is open and transparentopens in a new tab or window, shared data and research, and "made the greatest contribution to global origins research." The National Health Commission, China's top medical authority, said the country "invested huge manpower, material, and financial resources" and "has not stopped looking for the origins of the coronavirus."

It could have played out differently, as shown by the outbreak of SARSopens in a new tab or window, a genetic relative of COVID-19, nearly 20 years ago. China initially hid infections then, but WHO complained swiftly and publicly. Ultimately, Beijing fired officials and made reforms. The U.N. agency soon found SARS likely jumped to humans from civet cats in southern China and international scientists later collaborated with their Chinese counterparts to pin down bats as SARS' natural reservoir.

But different leaders of both China and WHO, China's quest for control of its researchers, and global tensions have all led to silence when it comes to searching for COVID-19's origins. Governments in Asia are pressuring scientists not to look for the virus for fear it could be traced inside their borders.

Even without those complications, experts say identifying how outbreaks begin is incredibly challenging and that it's rare to know with certainty how some viruses begin spreading.

"It's disturbing how quickly the search for the origins of [COVID-19] escalated into politics," said Mark Woolhouse, PhD, a University of Edinburgh outbreak expert. "Now this question may never be definitively answered."

Clouds of Secrecy

Secrecy clouds the beginning of the outbreak. Even the date when Chinese authorities first started searching for the origins is unclear.

The first publicly known search for the virus took place on Dec. 31, 2019, when Chinese Center for Disease Control (CDC) scientists visited the Wuhan market where many early COVID-19 cases surfaced.

However, WHO officials heard of an earlier inspection of the market on Dec. 25, 2019, according to a recording of a confidential WHO meeting provided to AP by an attendee. Such a probe has never been mentioned publicly by either Chinese authorities or WHO.

In the recording, WHO's top animal virus expert, Peter Ben Embarek, PhD, mentioned the earlier date, describing it as "an interesting detail." He told colleagues that officials were "looking at what was on sale in the market, whether all the vendors have licenses, [and] if there was any illegal [wildlife] trade happening in the market."

A colleague asked Ben Embarek, who is no longer with WHO, if that seemed unusual. He responded that "it was not routine," and that the Chinese "must have had some reason" to investigate the market. "We'll try to figure out what happened and why they did that."

Ben Embarek declined to comment. Another WHO staffer at the Geneva meeting in late January 2020 confirmed Ben Embarek's comments.

The AP could not confirm the search independently. It remains a mystery if it took place, what inspectors discovered, or whether they sampled live animals that might point to how COVID-19 emerged.

A Dec. 25, 2019, inspection would have come when Wuhan authorities were aware of the mysterious disease. The day before, a local doctor sent a sample from an ill market vendoropens in a new tab or window to get sequenced that turned out to contain COVID-19. Chatter about the unknown pneumonia was spreading in Wuhan's medical circles, according to one doctor and a relative of another who declined to be identified, fearing repercussions.

A scientist in China when the outbreak occurred said they heard of a Dec. 25 inspection from collaborating virologists in the country. They declined to be named out of fear of retribution.

WHO said in an email that it was "not aware" of the Dec. 25 investigation. It is not included in the U.N. health agency's official COVID-19 timelineopens in a new tab or window.

When China CDC researchers from Beijing arrived on Jan. 1 to collect samples at the market, it had been ordered shut and was already being disinfected, destroying critical information about the virus. Gao Fu, PhD, then head of the China CDC, mentioned it to an American collaborator.

"His complaint when I met him was that all the animals were gone," said Columbia University epidemiologist Ian Lipkin, MD, PhD.

Robert Garry, PhD, who studies viruses at Tulane University, said a Dec. 25 probe would be "hugely significant," given what is known about the virus and its spread.

"Being able to swab it directly from the animal itself would be pretty convincing and nobody would be arguing" about the origins of COVID-19, he said.

But perhaps local officials simply feared for their jobs, with memories of firings after the 2003 SARS outbreak still vivid, said Ray Yip, MD, MPH, the founding head of the U.S. CDC outpost in China.

"They were trying to save their skin, hide the evidence," Yip said.

The Wuhan government did not respond to a faxed request for comment.

Another early victim was Zhang Yongzhen, the first scientist to publish a sequence of the virusopens in a new tab or window. A day after he wrote a memo urging health authorities to take action, China's top health official ordered Zhang's lab closed.

"They used their official power against me and our colleagues," Zhang wrote in an email provided to AP by Edward Holmes, PhD, an Australian virologist.

On Jan. 20, 2020, a WHO delegation arrived in Wuhan for a 2-day mission. China did not approve a visit to the market, but they stopped by a China CDC lab to examine infection prevention and control procedures, according to an internal WHO travel report. WHO's then-China representative, Gauden Galea, MD, told colleagues in a private meeting that inquiries about COVID-19's origins went unanswered.

By then, many Chinese were angry at their governmentopens in a new tab or window. Among Chinese doctors and scientists, the sense grew that Beijingopens in a new tab or window was hunting for someone to blame.

"There are a few cadres who have performed poorly," Chinese leader Xi Jinping said in unusually harsh commentsopens in a new tab or window in February. "Some dare not take responsibility, wait timidly for orders from above, and don't move without being pushed."

The government opened investigations into top health officials, according to two former and current China CDC staff, and three others familiar with the matter. Health officials were encouraged to report colleagues who mishandled the outbreak to Communist Party disciplinary bodies, according to two of the people.

Some people both inside and outside China speculated about a laboratory leak. Those suspicious included right-wing American politiciansopens in a new tab or window, but also researchers close to WHO.

The focus turned to the Wuhan Institute of Virology, a high-level lab that experimented with some of the world's most dangerous viruses.

In early February 2020, some of the West's leading scientists, headed by Jeremy Farrar, MD, PhD, then at Britain's Wellcome Trust, and Anthony Fauci, MD, then director of the U.S. National Institute of Allergy and Infectious Diseases at NIH, banded together to assess the origins of the virus in calls, a Slack channel, and emails.

They drafted a paper suggesting a natural evolution, but even among themselves, they could not agree on the likeliest scenario. Some were alarmed by features they thought might indicate tinkering.

"There have [been] suggestions that the virus escaped from the Wuhan lab," Holmes, the Australian virologist, who believed the virus originated in nature, wrote in a Feb. 7, 2020, email. "I do a lot of work in China, and I can [assure] you that a lot of people there believe they are being lied to."

American scientists close to researchers at the Wuhan Institute of Virology warned counterparts there to prepare.

James LeDuc, PhD, head of a Texas lab, emailed his Wuhan colleague on Feb. 9, 2020, saying he'd already been approached by U.S. officials. "Clearly addressing this will be essential, with any kind of documentation you might have," he wrote.

The Chinese government was conducting its own secret investigation into the Wuhan Institute. Gao, the then-head of the China CDC, and another Chinese health expert revealed its existence in interviews months and years lateropens in a new tab or window. Both said the investigation found no evidence of wrongdoing, which Holmes, the Australian virologist, also heard from another contact in China. But Gao said even he hadn't seen further detailsopens in a new tab or window, and some experts suspect they may never be released.

WHO started negotiations with China for a further visit with the virus origins in mind, but it was China's Foreign Ministry that decided the terms.

Scientists were sidelined and politicians took control. China refused a visa for Ben Embarek, then WHO's top animal virus expert. The itinerary dropped nearly all items linked to an origins search, according to draft agendas for the trip obtained by the AP. And Gao, the then-head of the China CDC who is also a respected scientist tasked with investigating the origins, was left off the schedule.

Instead, Liang Wannian, PhD, a politician in the Communist Party hierarchy, took charge of the international delegation. Liang is an epidemiologist close to top Chinese officials and China's Foreign Ministry who is widely seen as pushing the party lineopens in a new tab or window, not science-backed policies, according to nine people familiar with the situation who declined to be identified to speak on a sensitive subject.

Liang ruled in favor of shutting the Wuhan market at the beginning of the outbreak, according to a Chinese media interview with a top China CDC official that was later deletedopens in a new tab or window. Significantly, it was Liang who promoted an implausible theory that the virus came from contaminated frozen foodopens in a new tab or window imported into China. Liang did not respond to an emailed request for comment.

Most of the WHO delegation was not allowed to go to Wuhan, which was under lockdown. The few who did learned little. They again had no access to the Wuhan Institute of Virology or the wildlife market and obtained only scant details about China CDC efforts to trace the coronavirus there.

On the train, Liang lobbied the visiting WHO scientists to praise China's health response in their public report. Bruce Aylward, MD, a senior adviser to WHO Director-General Tedros Adhanom Ghebreyesus, PhD, saw it as the "best way to meet China's need for a strong assessment of its response."

The new section was so flattering that colleagues emailed Aylward to suggest he "dial it back a bit."

"It is remarkable how much knowledge about a new virus has been gained in such a short time," read the final report, which was reviewed by China's top health official before it went to Tedros.

As criticism of China grew, the Chinese government deflected blame. Instead of firing health officials, they declared their virus response a success and closed investigations into the officials with few job losses.

"There were no real reforms, because doing reforms means admitting fault," said a public health expert in contact with Chinese health officials who asked not to be identified because of the sensitivity of the matter.

In late February 2020, the internationally respected doctor Zhong Nanshan, MD, appeared at a news conferenceopens in a new tab or window and said that "the epidemic first appeared in China, but it did not necessarily originate in China."

Days later, Chinese leader Xi ordered new controls on virus researchopens in a new tab or window. A leaked directive from China's Publicity Department ordered media not to report on the virus origins without permissionopens in a new tab or window, and a public WeChat account reposted an essay claiming the U.S. military created COVID-19 at a Fort Detrick lab and spread it to China during a 2019 athletic competition in Wuhan. Days later, a Chinese Foreign Ministry spokesperson repeated the accusationopens in a new tab or window.

The false claims enraged U.S. President Donald Trump, who began publicly blaming China for the outbreak, calling COVID-19 "the China virus" and the "kung-flu."opens in a new tab or window

Chinese officials told WHO that blood tests on lab workers at the Wuhan Institute of Virology were negative, suggesting they hadn't been previously infected with bat coronaviruses. But when WHO pressed for an independent audit, Chinese officials balked and demanded WHO investigate the U.S. and other countries as well.

By blaming the U.S., Beijing diverted blame. It was effective in Chinaopens in a new tab or window, where many Chinese were upset by racially charged criticism. But outside China, it fueled speculation of a lab-leak cover-up.

By the time WHO led another visit to Wuhanopens in a new tab or window in January 2021, a year into the pandemic, the atmosphere was toxic.

Liang, the Chinese health official in charge of two earlier WHO visits, continued to promote the questionable theory that the virus was shipped into China on frozen food. He suppressed information suggesting it could have come from animals at the Wuhan market, organizing market workers to tell WHO experts no live wildlife was sold and cutting recent photos of wildlife at the market from the final report. There was heavy political scrutiny, with numerous Chinese officials who weren't scientists or health officers present at meetings.

Despite a lack of direct access, the WHO team concludedopens in a new tab or window that a lab leak was "extremely unlikely." So it came as an infuriating surprise to Chinese officials when, months later, WHO chief Tedrosopens in a new tab or window said that it was "premature"opens in a new tab or window to rule out the lab-leak theory, saying such lab accidents were "common," and pressed China to be more transparent.

China told WHO any future missions to find COVID-19 origins should be elsewhere, according to a letter obtained by AP. Since then, global cooperation on the issue has ground to a halt; an independent group convened by WHO to investigate the origins of COVID-19 in 2021 has been stymied by the lack of cooperation from China and other issues.

Chinese scientists are still under heavy pressure, according to 10 researchers and health officials. Researchers who published papers on the coronavirus ran into trouble with Chinese authorities. Others were barred from travel abroad for conferences and WHO meetings. Gao, the then-director of the China CDC, was investigated after President Biden ordered a reviewopens in a new tab or window of COVID-19 data, and again after giving interviews on the virus origins.

New evidence is treated with suspicion. In March 2023, scientists announced that genetic material collected from the market showed raccoon dog DNAopens in a new tab or window mixed with COVID-19 in early 2020, data that WHO said should have been publicly shared years before. The findings were posted, then removed by Chinese researchers with little explanation.

The head of the China CDC Institute of Viral Disease was forced to retire over the release of the market data, according to a former China CDC official who declined to be named to speak on a sensitive topic.

"It has to do with the origins, so they're still worried," the former official said. "If you try and get to the bottom of it, what if it turns out to be from China?"

Other scientists note that any animal from which the virus may have originally jumped has long since disappeared.

"There was a chance for China to cooperate with WHO and do some animal sampling studies that might have answered the question," said Tulane University's Garry. "The trail to find the source has now gone cold."


https://www.medpagetoday.com/infectiousdisease/covid19/109771

Neurotechnology Development Must Be Slow and Steady

 Through my work as a neuroscientist who designs neural implants to monitor the injured brain after severe traumatic brain injuries, stroke, and brain cancers, it has become very clear to me that my field needs to communicate more directly and more often with general audiences. Neurotechnology research is becoming an increasingly important and mainstream part of the neuroscience field, and with that, disseminating information and implementing regulations is essential. Not doing so risks public distrust

opens in a new tab or window and the proliferation of misinformation at a time where we are seeing a boom in the development and translation of devices that interface with the brain and central nervous system.

The Toll of Neurological Disorders

In my role, I see how a closer relationship between man and machine could have transformative benefits for the treatment of various neurological disorders, which lead to an estimated 9 million deaths globallyopens in a new tab or window each year. This loss of life is bad enough on its own, but is further compounded by the number of people who have long-term disability because of brain injuries, disorders, and neurodegeneration. Neurological disorders are the leading causeopens in a new tab or window of disability adjusted life years (DALYs) lost, which have increased a whopping 18% since 1990. In the aftermath of a neurological diagnosis or incident, people may lose their ability to provide or care for themselves, and walk or even talk, and the impact is felt personally by the patient, as well as in families and communities.

We often simplify disease to a false dichotomy of survival and death, underplaying the impact of what happens to patients post-occurrence. This was highlighted most recently by the COVID-19 pandemic and ensuing reports of long COVID; initially, the voices of "long-haulers" were disregarded and many felt neglectedopens in a new tab or window. We now understand there's a connection between long COVID and neurological sequelaeopens in a new tab or window. We need new tools to combat the prevalence of these conditions, both as they relate to COVID and more broadly.

This is where devices that interface with the brain, such as brain computer interfaces (BCIs), can excel.

The Potential of Neurotechnology

Deployed in the correct manner, future BCIs have the potential to enable their users to control computers with their thoughts after loss of function. This could be life-changing for millions of patients with conditions such as locked-in syndrome, amyotrophic lateral sclerosis (ALS), or tetraplegia. Clinical research and testing of devices for various conditionsopens in a new tab or window is ongoing, and several companiesopens in a new tab or window have made significant stridesopens in a new tab or window to bring these devicesopens in a new tab or window toward commercialization and reaching patients.

In academic research, we have seen the demonstration of a brain-spine interfaceopens in a new tab or window to restore a person's ability to walk after a serious car accident, the decoding of neural signals to facilitate speechopens in a new tab or window, and the use of brain implants to control neuroprosthesesopens in a new tab or window. By implanting electrodes that can record the electrical signals that emanate from neurons and decoding the resulting information, users can passively or actively control computer systems to create desired outputs.

That being said, these devices and interventions are not without risks.

The Need to Regulate and Communicate

We have an incredible new frontier in which to innovate, but one that we should regulate immediately. As we begin to address the neurological disease burden, what are the boundaries? What risks are acceptable? What are the ethical concerns?

The for-profit startup Neuralinkopens in a new tab or window, one of the more well-known players in the development of BCIs, has the mission to "Create a generalized brain interface to restore autonomy to those with unmet medical needs today and unlock human potential tomorrow." While this may sound promising at face value, expertsopens in a new tab or window and policymakersopens in a new tab or window have raised safety concerns related to the company's interventions and trials. For-profit companies can do great things, but I worry that if profit is the priority, morals and ethics may quickly fade.

When it comes to neurotechnology of any kind, there is a major risk of harm that needs to be more widely discussed now, before such devices become mainstream.

Our current trajectory and history -- quickly embracing social media, AI, and smart devices -- suggest that we won't be able to resist the temptation to augment ourselves with neurotechnology, due to an insatiable desire to "progress." But look at other examples: the dangers of smartphones are nearly as numerous as their virtues. We are already playing catch up with the mental health consequences of our increased connectedness to social networksopens in a new tab or window through smartphones, not to mention their impact on our sleepopens in a new tab or windowbrain developmentopens in a new tab or window, and self-esteem. Tech advancement comes with positives and negatives. The importance, therefore, of checks and balances for any emerging technology should be part of the process of its development and maturation.

And, at least when it comes to smartphones, people interacting with them can unplug, turn them off, or otherwise moderate their interaction level. How can patients do that when the technology is located within their bodies?

There's an infinite number of other questions: What are the limits on determining who will benefit from neurotechnology? Can we protect such systems from weaponizationopens in a new tab or window? What about consent? Will we create more inequality from devices that were originally intended to facilitate equity? Hackingopens in a new tab or windowprivacyopens in a new tab or window, altered perception -- you name it. BCIs employed in the wrong way could very easily be abused. The placement and long-term implantation of such devices also risks injury, infectionopens in a new tab or window, and lasting damage. The general public needs to be aware of the risks.

A Path Forward

I believe that limiting the use of BCIs to restoring function for those with injuries and disorders, and supporting individuals with disability, is not a concession but a bold way forward. Physically connecting our brains to BCIs purely to augment ourselves as human beings seems like an area of serious ethical concern. Other fields, such as roboticsopens in a new tab or window and AIopens in a new tab or window, have begun to consider and set their boundaries, the same should be done with BCIsopens in a new tab or window.

BCIs have the power to transform the lives of those with neurological disorders and long-term disability. We have an opportunity to be proactive by addressing the ethical and brain-altering challenges inherent in BCIs now. The scientific community needs to get ahead of this potentially disruptive technology, inform the general public and patients, and create safeguards. Let's not make today's solutions tomorrow's problems.

De-Shaine Murray, PhD, MSCI, MRes,opens in a new tab or window is a Wu Tsai Institute postdoctoral fellow at Yale University, Black in Neuro co-founder, and development director and a Public Voices Fellow of the OpEd Project.

https://www.medpagetoday.com/opinion/second-opinions/109775

Boehringer, Ochre Bio Team in Potential $1B Deal to Develop Regenerative Liver Drugs

 Boehringer Ingelheim has struck a deal with Ochre Bio, announcing Monday an agreement potentially worth more than $1 billion to collaborate on treatments for liver diseases such as late-stage metabolic dysfunction-associated steatohepatitis cirrhosis.

Madrigal Pharmaceuticals recently won FDA approval for Rezdiffra (resmetirom) in metabolic dysfunction-associated steatohepatitis (MASH) and rivals are following close behind. However, Rezdiffra and other leading R&D programs target patients before they develop cirrhosis. There remains a need for therapies that can slow or reverse the progression of disease in later-stage patients, either to help them survive until a donor organ is available or eliminate the need for a transplant altogether.

Boehringer has identified Ochre as a partner that can help discover such therapies. The German pharma company has agreed to pay $35 million in upfront and near-term research-based milestone payments to collaborate with Ochre. The near-term fees are part of a broader financial package that could be worth more than $1 billion if the project hits its clinical, regulatory and commercial milestones.

In return for the outlay, Boehringer has secured the chance to work with Ochre to identify and validate regenerative targets for chronic liver diseases. The goal is to boost the liver’s ability to self-repair, which is diminished in patients with late-stage disease, while preventing or reversing disease progression.

Ochre has used funding from investors including Khosla Ventures to build its R&D platform. Working out of sites in the U.K., Taiwan and New York, Ochre is developing RNA therapies to treat liver disease. The biotech’s technology is built on a deep phenotyping approach that uses cellular genomics, tissue imaging and machine learning to reveal interactions between genes and cells. Ochre is applying its technology to liver samples, living micro-liver slices and whole living perfused livers.

Insights generated using the platform will help inform development of RNA therapies. The development side of Ochre’s operation is focused on two challenges: getting RNA to the right cell type and modulating the duration of effect.

GalNAc conjugates, a sugar molecule that can recognize and bind to a cell surface protein which is abundantly expressed on liver cells (hepatocytes), can already get RNA to the liver but they only target one of several cell types in the organ. New approaches are needed to deliver RNA to cells other than hepatocytes. Ochre is conjugating its RNA therapies to different ligands to enable delivery to other types of liver cells, such as Kupffer cells.

At the same time, Ochre is exploring how chemical modifications modulate the duration of effect. The ability to alter the duration of effect sets Ochre apart from rivals that are using CRISPR to treat liver disease by permanently editing genes. CRISPR lacks the flexibility of Ochre’s RNA-based approach but enables one-shot therapies that can free patients from the need for ongoing treatment.

https://www.biospace.com/article/boehringer-teams-with-ochre-bio-in-potential-1b-deal-to-develop-regenerative-liver-drugs/