After Casgevy Follows A Genome Editing Bevy

Today, December 8, 2023, the United States Food and Drug Administration ("FDA") emulated its British equivalent, the Medicines and Healthcare products Regulatory Agency, by approving the CRISPR/Cas9-based therapy Casgevy, a gene editing treatment for sickle cell disease ("SCD").  As it did in the United Kingdom, this approval marks a milestone in therapeutic history in the United States.   Here is how the FDA described Casgevy:

Casgevy, a cell-based gene therapy, is approved for the treatment of sickle cell disease in patients 12 years of age and older with recurrent vaso-occlusive crises. Casgevy is the first FDA-approved therapy utilizing CRISPR/Cas9, a type of genome editing technology. Patients’ hematopoietic (blood) stem cells are modified by genome editing using CRISPR/Cas9 technology.

CRISPR/Cas9 can be directed to cut DNA in targeted areas, enabling the ability to accurately edit (remove, add, or replace) DNA where it was cut. The modified blood stem cells are transplanted back into the patient where they engraft (attach and multiply) within the bone marrow and increase the production of fetal hemoglobin (HbF), a type of hemoglobin that facilitates oxygen delivery. In patients with sickle cell disease, increased levels of HbF prevent the sickling of red blood cells.

The FDA was impressed by the strong performance of Casgevy in clinical trials:

The safety and effectiveness of Casgevy were evaluated in an ongoing single-arm, multi-center trial in adult and adolescent patients with SCD. Patients had a history of at least two protocol-defined severe VOCs during each of the two years prior to screening. The primary efficacy outcome was freedom from severe VOC episodes for at least 12 consecutive months during the 24-month follow-up period. A total of 44 patients were treated with Casgevy. Of the 31 patients with sufficient follow-up time to be evaluable, 29 (93.5%) achieved this outcome. All treated patients achieved successful engraftment with no patients experiencing graft failure or graft rejection. 

The most common side effects were low levels of platelets and white blood cells, mouth sores, nausea, musculoskeletal pain, abdominal pain, vomiting, febrile neutropenia (fever and low white blood cell count), headache and itching.

The FDA granted the license for Casgevy to biotechnology firm, Vertex Pharmaceuticals Inc..  However, many other biotechnology and pharmaceutical companies are waiting in the line for the FDA to grant approval to their genome editing therapies. 

Clonan the Barbarian and the Mastiff Landslide

 Argentina voted overwhelmingly on November 19, 2023, for Javier Milei to become its next president.  President Milei has a fascinating biography, which includes having played goalie for the Club Atlético Chacarita junior team, sung for the Rolling Stones cover band Everest, taught economics in universities for more than two decades, and hosted his own radio show.  Even more fascinating, however, are his dogs.  As of his election as president, he had five English Mastiffs.  Not only are four named for Milei's favourite three economists (that is, Milton Friedman, Murray Rothbard, and Robert Lucas), they are also reputed to be clones of his first English Mastiff, Conan.

It may or may not be true that all politicians are alike.  However, Milei's English Mastiffs are all extremely similar, which is unsurprising given their apparent provenance as clones.

Medicine's CRISPR Focus

 The United Kingdom Medicines and Healthcare products Regulatory Agency ("MHRA") made history today when it approved the medicine "Casgevy" for the treatment of sickle-cell disease and transfusion-dependent β-thalassemia in patients aged 12 and older.  As the MHRA announced in a press release,

Casgevy is the first medicine to be licensed that uses the innovative gene-editing tool CRISPR, for which its inventors were awarded the Nobel Prize in 2020.  

Both sickle cell disease and β-thalassemia are genetic conditions caused by errors in the genes for haemoglobin, which is used by red blood cells to carry oxygen around the body. Sickle cell disease is particularly common in people with an African or Caribbean family background. β-thalassemia mainly affects people of Mediterranean, south Asian, southeast Asian and Middle Eastern origin. 

In people with sickle cell disease, this genetic error can lead to attacks of very severe pain, serious and life-threatening infections, and anaemia (whereby your body has difficulty carrying oxygen). 

In people with β-thalassaemia, it can lead to severe anaemia. Patients often need a blood transfusion every 3 to 5 weeks, and injections and medicines throughout their lives. 

Casgevy is designed to work by editing the faulty gene in a patient’s bone marrow stem cells so that the body produces functioning haemoglobin. To do this, stem cells are taken out of bone marrow, edited in a laboratory and then infused back into the patient after which the results have the potential to be life-long. 

Here's how Casgevy, developed by Vertex Pharmaceuticals in Boston, Massachusetts, and CRISPR Therapeutics in Zug, Switzerland, works:

Casgevy is administered by taking stem cells out of a patient’s bone marrow and editing a gene in the cells in a laboratory. Patients must then undergo conditioning treatment to prepare the bone marrow before the modified cells are infused back into the patient. After that, patients may need to spend at least a month in a hospital facility while the treated cells take up residence in the bone marrow and start to make red blood cells with the stable form of haemoglobin.

Sickle-cell disease and transfusion-dependent β-thalassemia are painful and debilitating conditions that disproportionately afflict the poor.  Casgevy marks a landmark, heralding the beginning of CRISPR-based therapeutics approved for the market, and, more importantly, for the treatment of patients. 

COPs And Robbers

 The 27th Conference of the Parties ("COP 27") to the Framework Convention on Climate Change ("FCCC") wrapped up several days late, on November 20, 2022, and myriad dollars short of those needed to limit global warning to 1.5°C.  Buried within its dense diplomatic verbiage, the "Draft decision" negotiated at COP 27 features two notable statements.  First, the goal of limiting global mean temperature rise to 1.5 °C remains squishy, with the parties not committing, but "resolv[ing] to pursue further efforts to limit the temperature increase to 1.5 °C" (Draft decision, I(7)).  Second, section VI of the Draft decision, entitled "Loss and damage", contemplates de facto liability by rich countries for damages caused to poorer countries by the effects of climate change.  To a betting person, the odds the world will exceed the "limit" of 1.5 °C would now seem to have shortened.  Meanwhile, the odds rich countries will come anywhere close to committing the financial resources necessary to meet the spirit of the new "loss and damage" obligation will surely start off as very long.

There is a silver lining to the Draft decision reached at COP 27:  once the 400 or so private jets that flew climate delegates and lobbyists to the negotiations depart, the carbon footprint of the host city, Sharm el-Sheikh, is likely to settle back down to its usual level.

ALI

I'm deeply honoured to have been elected a member of the American Law Institute ("ALI") in July 2022. I look forward to doing my best to contribute to the important mission of this wonderful organization:  “to promote the clarification and simplification of the law and its better adaptation to social needs, to secure the better administration of justice, and to encourage and carry on scholarly and scientific legal work.”

Twin Royalties Paradox

 The Supreme Court of Canada clarified the Canadian Copyright Act (R.S.C., 1985, c. C-42) when it rendered its judgment in Society of Composers et al. v. Entertainment Software Association on July 15, 2022.  At issue was whether the Copyright Act added a new legal right for authors by amending §3(1)(f), which grants to authors the right "to communicate the work to the public by telecommunication", when the Canadian Parliament attempted to incorporate Article 8 of the WIPO Copyright Treaty into the Copyright Act.  The Copyright Board of Canada had earlier ruled that §2.4(1.1) had modified §3(1)(f) in such a way as to require that users of works of authorship "needed to pay two royalties to access works online - a royalty for "making works available" and an additional royalty when the work was actually downloaded or streamed."  The Federal Court of Appeal overturned the Copyright Board, holding that there is no independent royalty simply for making a work available.  The Supreme Court broadly agreed, explaining,

If a work is downloaded or made available for downloading, §3(1)(f) is not engaged.  If a work is made available for streaming and later streamed, §3(1)(f) is only engaged once.

In addition to its decision finding no additional "making available" royalty, the Supreme Court decided to other issues.  One involved the appropriate standard of review.  The other considered how international treaties, such as the WIPO Copyright Treaty, should contribute to the interpretation of statutory provisions intended to implement such treaties into national law.  Although the Supreme Court noted that "A treaty should be considered when interpreting statutes that purport to implement the treaty", and that "There is no need to find textual ambiguity in a statute before considering the treaty", a court must "intepret what the legislature (federally or provincially) has enacted and not subordinate this to what federal executive has agreed to internationally."  In short, "It is always the domestic statute that governs".

Just as Aristotle may have observed that a friend is "One soul dwelling in two bodies", Society of Composers et al. v. Entertainment Software Association suggests that online copyright may be one royalty dwelling in two legal rights.

Fair Share

My brilliant and creative colleagues, Bill Tomlinson, Bonnie Nardi, Daniel Stokols, Ankita Raturi, and I are pleased our article, "Returning ecological wealth to nonhuman species through design: the case for ecosystemas", has been published in Ecology and Society (27(2): 34).  Here is the abstract:

Human population and energy use have increased rapidly in recent centuries. This growth has relied on Homo sapiens appropriating ecosystem services previously shared more equitably with many other species. Envisioning this process as a transfer of ecological wealth among species provides a framework within which to examine human activities. We use this framework to critique the broad endeavor of design, and in particular human-computer interaction design, as it has been pursued by human civilization over the past several decades. We offer a conceptual tool, the ecosystema, that may help enable design processes to support the redistribution of ecological wealth to nonhuman species. The ecosystema is based on the concept of personas: distilled representations of particular user groups that are a key part of many design processes. The ecosystema construct is analogous to a persona, but at the level of an entire ecosystem rather than of a particular human population. This construct could help discern ecosystem level impacts and enable them to influence design processes more effectively. Ecosystemas also may afford greater leverage for effectively managing current environmental crises than existing anthropocentric design approaches.

Our article is available as a free PDF here.

Biotechnology Patent Law Top Ten Of 2020

Brilliant legal eagle, Kevin Noonan, and I collaborate each year on an article covering what we consider to be the top ten United States biotechnology patent law judicial decisions of that year.  Our article, "Biotechnology Patent Law Top Ten of 2020: Valeant Victorious, Falling Eagle, and Successful Slayback", was recently published in the Texas A & M Journal of Property Law (citation:  8 Tex. A&M J. Prop. L. 409-472 (2022)).  Download the article here for free.  Here is the abstract:

One of the most famous trilogies ever published ends with the hero, Frodo the hobbit, sailing aboard an elven ship from the Grey Havens of Middle Earth to the Undying Lands in the west. Despite this being the third in a series of “Biotechnology Patent Law Top Ten” articles, in this trilogy the world of biotechnology patent law has no leading hero, no ultimate destination, nor any final resolution of issues.

To the contrary, this exciting area of law and technology continues to witness winners and losers in myriad battles across a wide doctrinal theatre of legal war with no end in sight. It is true that some in biotechnology view the uncertainty surrounding the scope of patentable biotechnological subject matter under 35 U.S.C. § 101 as a metaphorical ring they wish the fires of Mount Doom could destroy (or at least clarified by the United States Supreme Court). Others consider the ongoing patent disputes between the University of California, University of Vienna, and Emmanuelle Charpentier (often referred to collectively as “CVC”) and the Broad Institute of MIT and Harvard to be as consequential as the Battle of the Five Armies. We will not even try to compare the endless Abbreviated New Drug Application (“ANDA”) struggles between brand pharmaceutical companies and their upstart generic drug firm rivals using a literary device derived from The Lord of the Rings.3 Suffice it to say that biotechnology patent law will continue to vigorously evolve, and we plan to continue our coverage of its evolution beyond the current trilogy of Biotechnology Patent Law Top Tens.

As in previous years, we admit it was difficult to choose precisely ten top biotechnology patent law decisions. There are certainly otherswe did not include that warrant close attention for their reasonings, rules, and future implications. Nevertheless, both we and our readers can count, so we have done our best to select what we consider to be the top ten biotechnology patent law decisions of 2020. We discuss these decisions [in the article].

To avoid falling behind, consider reading the 2020 Top Ten promptly, because publication of our Biotechnology Patent Law Top Ten of 2021 is imminent.

Burke's Bees

 The Burke Museum of Natural History and Culture is a hidden gem in Seattle.  Nestled in the northwesternmost corner of the University of Washington campus, right next to the School of Law, its collections and research efforts are both excellent.  As Visiting Professor at the School of Law back in 2011, I would often cross the 100m to the Burke to explore its latest exhibits.  The Burke has now assured its excellence by appointing the brilliant and inspiring bee expert Dr. Gabriela Chavarria as Executive Director.

Omicron May Be O-Mega

 Excellent as usual, Dr. Roby Bhattacharyya, of the Broad Institute of MIT and Harvard released his "Broad COVID update:  Omicron edition" on December 17, 2021.  Here it is:

The Omicron variant of SARS-CoV-2 may not be "micron" at all, but, rather, Omega.  Let's hope a viral tidal wave is not on its way.