A low-pro­file biotech bests Re­gen­eron in high-pro­file patent suit

For near­ly a decade now, the low-pro­file Cam­bridge biotech Kymab has been bat­tling in US, UK, Japan­ese and Aus­tralian courts with the biotech be­he­moth Re­gen­eron.

Re­gen­eron has turned it­self in­to a $70 bil­lion com­pa­ny off of a plat­form of trans­geni­cal­ly hu­man­ized mice they can use to make an­ti­bod­ies for any­thing from Ebo­la to col­orec­tal can­cer. The tech­nol­o­gy took decades and bil­lions to build, 20 years from the com­pa­ny’s found­ing to the first ap­proved drug. And the com­pa­ny guards and touts it zeal­ous­ly, break­ing their pro­duc­tion process down in­to var­i­ous brand­ed com­po­nents — Ve­locim­mune, Ve­loci­gene, Ve­loci­mouse and four oth­er Ve­locis — and some­times su­ing would-be copy­cats. In 2014, most no­tably, they sued two Pfiz­er-backed en­ti­ties for patent in­fringe­ment.

The year be­fore those suits, though, Re­gen­eron al­leged in the Eu­ro­pean High Court that Kymab had in­fringed on a patent they had filed in 2012 around ways of ge­net­i­cal­ly mod­i­fy­ing a mouse. It was the first of sev­er­al dif­fer­ent patent suits be­tween the com­pa­nies. Sev­en years lat­er, that fight is still on­go­ing — a UK Supreme Court de­ci­sion is pend­ing — but Kymab has just won the lat­est sal­vo. The US Patent Tri­al and Ap­peal Board (PT­AB) re­ject­ed in April Re­gen­eron’s re­quest to in­val­i­date 4 Kymab patents, and to­day they re­ject­ed a fifth one.

The case could have im­pact both broad­ly on how biotechs choose to patent their in­ven­tions and specif­i­cal­ly on Kymab, a com­pa­ny that, af­ter rais­ing over $220 mil­lion, is now in the ear­ly clin­i­cal stage and in­di­cat­ed its in­ter­est last year for a US IPO.

Kymab has its own name for their hu­man­ized mice: Ky­mouse. Spun out of the Well­come Trust’s ge­net­ics-fo­cused Sanger In­sti­tute, the com­pa­ny was found­ed in 2010 and their plat­form works sim­i­lar­ly to Re­gen­eron: in­fect a mouse with a virus, for in­stance, and in­stead of murine an­ti­bod­ies, the mouse will cre­ate hu­man an­ti­bod­ies that in the­o­ry can then be giv­en to a pa­tient. The com­pa­ny un­veiled the plat­form in a 2014 Na­ture Biotech­nol­o­gy pa­per.

By 2015, the two com­pa­nies were in patent dis­putes in four dif­fer­ent coun­tries. At the cen­ter of the case were patents Re­gen­eron had placed on a so­lu­tion to a tricky prob­lem mak­ing trans­genic mice. Rough­ly, the first at­tempts to reap hu­man an­ti­bod­ies from ge­net­i­cal­ly mod­i­fied mice had failed be­cause when you give a mouse a ful­ly hu­man im­mune sys­tem, the mouse be­comes “im­muno­log­i­cal­ly sick,” mean­ing it can’t mount as force­ful an im­mune re­sponse and gen­er­ate as many an­ti­bod­ies as a nor­mal, mousi­fied mouse would.

Re­gen­eron fig­ured out that you pre­vent this im­muno­log­i­cal short­fall by leav­ing cer­tain mouse DNA se­quences in­tact and swap­ping them out of the an­ti­bod­ies be­fore you give them to pa­tients. The tech­ni­cal term for this is a “re­verse chimeric lo­cus.” Kymab al­so us­es re­verse chimeric lo­cus to cre­ate their an­ti­bod­ies.

While al­leg­ing Kymab in­fringed on their patents in Eu­rope, in the US, Re­gen­eron al­leged that Kymab’s an­ti­body patents should be thrown out on the grounds that they were an “ob­vi­ous” ex­ten­sion of Re­gen­eron’s work. In April, the PT­AB up­held a pre­vi­ous rul­ing that 4 of Kymab’s patents were valid. To­day’s rul­ing up­held the va­lid­i­ty of the fifth and fi­nal patent in dis­pute.

With the Japan suit over and an Aus­tralian court re­cent­ly rul­ing in fa­vor of Kymab, the last domi­no is in the UK, where Re­gen­eron ar­gued that Kymab’s mice in­fringed on their patent­ed strat­e­gy. Kymab ar­gued that Re­gen­eron’s patents did not give easy in­struc­tion for an ex­pert to car­ry out the pro­tect­ed sci­ence – as patents must. A 2016 rul­ing sided with Kymab, a 2018 rul­ing with Re­gen­eron, and in Feb­ru­ary, the UK Supreme Court heard the case. Both com­pa­nies now await their ver­dict.

Donald and Melania Trump watch the smoke of fireworks from the South Lawn of the White House on July 4, 2020 (via Getty)

Which drug de­vel­op­ers of­fer Trump a quick, game-chang­ing ‘so­lu­tion’ as the pan­dem­ic roars back? Eli Lil­ly and Ab­Cellera look to break out of the pack

We are unleashing our nation’s scientific brilliance and will likely have a therapeutic and/or vaccine solution long before the end of the year.

— Donald Trump, July 4

Next week administration officials plan to promote a new study they say shows promising results on therapeutics, the officials said. They wouldn’t describe the study in any further detail because, they said, its disclosure would be “market-moving.”

— NBC News, July 3

Something’s cooking. And it’s not just July 4 leftovers involving stale buns and uneaten hot dogs.

Over the long weekend observers picked up signs that the focus in the Trump administration may swiftly shift from the bright spotlight on vaccines being promised this fall, around the time of the election, to include drugs that could possibly keep patients out of the hospital and take the political sting out of the soaring Covid-19 numbers causing embarrassment in states that swiftly reopened — as Trump cheered along.

So far, Gilead has been the chief beneficiary of the drive on drugs, swiftly offering enough early data to get remdesivir an emergency authorization and into the hands of the US government. But their drug, while helpful in cutting stays, is known for a limited, modest effect. And that won’t tamp down on the hurricane of criticism that’s been tearing at the White House, and buffeting the president’s most stalwart core defenders as the economy suffers.

We’ve had positive early-stage vaccine data, most recently from Pfizer and BioNTech, playing catchup on an mRNA race led by Moderna — where every little sign of potential trouble is magnified into a lethal threat, just as every advance excites a frenzy of support. But that race still has months to play out, with more Phase I data due ahead of the mid-stage numbers looming ahead. A vaccine may not be available in large enough quantities until well into 2021, which is still wildly ambitious.

So what about a drug solution?

Trump’s initial support for a panacea focused on hydroxychloroquine. But that fizzled in the face of data underscoring its ineffectiveness — killing trials that aren’t likely to be restarted because of a recent population-based study offering some support. And there are a number of existing drugs being repurposed to see how they help hospitalized patients.

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Elias Zerhouni (Photo by Vincent Isore/IP3/Getty Images)

Elias Zer­houni dis­cuss­es ‘am­a­teur hour’ in DC, the de­struc­tion of in­fec­tious dis­ease R&D and how we need to prep for the next time

Elias Zerhouni favors blunt talk, and in a recent discussion with NPR, the ex-Sanofi R&D and ex-NIH chief had some tough points to make regarding the pandemic response.

Rather than interpret them, I thought it would be best to provide snippets straight from the interview.

On the Trump administration response:

It was basically amateur hour. There is no central concept of operations for preparedness, for pandemics, period. This administration doesn’t want to or has no concept of what it takes to protect the American people and the world because it is codependent. You can’t close your borders and say, “OK, we’re going to be safe.” You’re not going to be able to do that in this world. So it’s a lack of vision, basically just a lack of understanding, of what it takes to protect the American people.

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George Yancopoulos (Regeneron)

UP­DAT­ED: Re­gen­eron co-founder George Yan­copou­los of­fers a com­bat­ive de­fense of the po­lice at a high school com­mence­ment. It didn’t go well

Typically, the commencement speech at Yorktown Central School District in Westchester — like most high schools — is an opportunity to encourage students to face the future with confidence and hope. Regeneron president and co-founder George Yancopoulos, though, went a different route.

In a fiery speech, the outspoken billionaire defended the police against the “prejudice and bias against law enforcement” that has erupted around the country in street protests from coast to coast. And for many who attended the commencement, Yancopoulos struck the wrong note at the wrong time, especially when he combatively challenged someone for interrupting his speech with a honk for “another act of cowardness.”

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Tesla and SpaceX founder Elon Musk gestures to the audience after being recognized by President Trump following the successful launch of a Falcon 9 rocket at the Kennedy Space Center. (via Getty Images)

Tes­la chief Elon Musk teams up with Covid-19 play­er Cure­Vac to build 'R­NA mi­cro­fac­to­ries'

Elon Musk has joined the global tech crusade now underway to revolutionize vaccine manufacturing — now aimed at delivering billions of doses of a new mRNA vaccine to fight Covid-19. And he’s cutting right to the front.

In a late-night tweet Wednesday, the Tesla chief announced:

Tesla, as a side project, is building RNA microfactories for CureVac & possibly others.

That’s not a lot to go on. But the tweet comes a year after Tesla’s German division in Grohmann and CureVac filed a patent on a “bioreactor for RNA in vitro transcription, a method for RNA in vitro transcription, a module for transcribing DNA into RNA and an automated apparatus for RNA manufacturing.” CureVac, in the meantime, has discussed a variety of plans to build microfactories that can speed up the whole process for a global supply chain.

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Sec­ond death trig­gers hold on Astel­las' $3B gene ther­a­py biotech's lead pro­gram, rais­ing fresh con­cerns about AAV

Seven months after Astellas shelled out $3 billion to acquire the gene therapy player Audentes, the biotech company’s lead program has been put on hold following the death of 2 patients taking a high dose of their treatment. And there was another serious adverse event recorded in the study as well, with a total of 3 “older” patients in the study affected.

The incidents are derailing plans to file for a near-term approval, which had been expected right about now.

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An ex­pe­ri­enced biotech is stitched to­geth­er from transpa­cif­ic parts, with 265 staffers and a fo­cus on ‘new bi­ol­o­gy’

Over the past few years, different teams at a pair of US-based biotechs and in labs in Japan have labored to piece together a group of cancer drug programs, sharing a single corporate umbrella with research colleagues in Japan. But now their far-flung operations have been knit together into a single unit, creating a pipeline with 10 cancer drug development programs — going from early-stage right into Phase III — and a host of discovery projects managed by a collective staff of some 265 people.

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New stan­dard of care? FDA hands Pfiz­er, Mer­ck KGaA an OK for Baven­cio in blad­der can­cer

The breakthrough therapy designation Pfizer and Merck KGaA notched for Bavencio in bladder cancer has quickly paved way for a full approval.

The PD-L1 drug is now sanctioned as a first-line maintenance treatment for patients with locally advanced or metastatic urothelial carcinoma, applicable in cases where cancer hasn’t progressed after platinum-containing chemotherapy.

Petros Grivas, the principal investigator of the supporting Phase III JAVELIN Bladder 100, called the approval “one of the most significant advances in the treatment paradigm in this setting in 30 years.”

On a roll, Mer­ck blazes through a new seg­ment of the bio­mark­er trail

Merck has notched an approval for using Keytruda to treat a biomarker-based subset of first-line colorectal cancer patients with unresectable or metastatic tumors, as the pharma giant continues to find new niches for its blockbuster PD-1 star.

The OK is significant in a number of ways. Not only does it build on an accelerated approval for all tumors characterized as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR); it also marks the first single treatment for colorectal cancer that doesn’t contain chemotherapy.

Vas Narasimhan, Novartis CEO (Patrick Straub/​EPA-EFE/​Shutterstock)

No­var­tis pays $678M for kick­back scheme as Vas Narasimhan tries to dis­tance phar­ma gi­ant from shady be­hav­ior

Novartis has reached another large settlement to resolve misconduct allegations, agreeing to pay more than $678 million to settle claims that it had spent hundreds of millions of dollars on lavish dinners, so-called speaking fees and expensive alcohol “that were nothing more than bribes” to get doctors to prescribe Novartis medications.

The top-shelf alcohol and lavish meals included a $3,250 per person night at Nobu in Dallas, a $672-per person dinner at Washington DC’s Smith & Wollensky and a $314 per person meal at Sushi Roku in Pasadena, according to the Justice Department complaint. There were at least 7 trips to Hooters and fishing trips in Alaska and off the Florida coast. Each of these events were supposed to be “speaker programs” where doctors educated other doctors on a drug, but the DOJ alleged many were “bogus” wine-and-dine events where the drug was barely mentioned, if at all.  (“Nobody presented slides on the fishing trips,” the complaint says.)