patentlaw

Are Pig Kidneys Patentable? The Legal Landscape Around The First Genetically Engineered Pig Kidney Transplant

/ Washington Journal of Law, Technology & Arts / Leave a comment

By: Bethany Butler

Last month, doctors at Massachusetts General Hospital successfully transplanted a genetically engineered pig kidney into a 64-year-old patient. Scientists removed porcine genes and added human genes via the CRISPR-Cas 9 gene editing technology. In total, sixty-nine of the pig’s genes were modified prior to transplantation. The surgery took approximately four hours, with the kidney functioning almost immediately after transplantation. eGenesis, a biotechnology company focused on genetically engineered, human-compatible organs, invented this procedure and the resulting genetically engineered kidney. This novel procedure may help to alleviate critical organ shortages in the US, with more than 100,000 Americans currently on the transplant wait list. Scientists hope this procedure will pave the way to more research and clinical applications that may help to alleviate the organ transplant shortage. 

The Legal Landscape

Novel research and clinical applications surrounding xenotransplantation, the transplanting of animal cells/organs to humans, have the potential to revolutionize access to life saving therapies. However, the legal landscape surrounding this science is far from settled. While areas of xenotransplantation of pig organs into humans have been granted patents, the procedure itself has not been approved by the FDA. These procedures, like the one used for the modified pig kidney transplant, are only currently able to move forward using “compassionate use” exceptions granted by the FDA. These exceptions apply to patients with life-threatening conditions where there is no alternative for treatment. 

Another important aspect of the law surrounding xenotransplantation is informed consent. Informed consent is a protection provided by the Health and Human Services regulation, 45 CFR Part 46. The regulation requires that important information, including any risks, be disclosed to the patient before he or she decides to participate in any trials or undergo treatment. Xenotransplantation procedures carry unique risks, such as zoonotic infections and the need for lifelong monitoring and intervention due to the nature of the procedure. Patients must be informed of and consent to all of the unique risks involved with these types of treatments. 

Xenotransplantation and Patent Law

Biological patents are generally utility patents, which allow the patent holder to exclude others from making, selling, using, or importing their biological invention for a specified period of time, currently twenty years in the United States. Companies like eGenesis can own biological patents for genetically modified animal organs and associated methods for xenotransplantation. Currently, these types of patents are protected by law, provided the claimed subject matter is not naturally occuring. US patent law has exceptions to patentable subject matter that are laws of nature, natural phenomena, and products of nature. The Supreme Court found, in the landmark case Association for Molecular Pathology v. Myriad Genetics, Inc., that “a naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated.” The case concerned whether the BRCA1 and BRCA2 genes can be patent eligible when isolated. These genes are responsible for tumor suppression and mutations in these genes commonly lead to the development of breast cancer. If the Supreme Court had ruled that Myriad Genetics could patent these gene sequences, that ruling would have effectively prevented any other company from offering diagnostic testing for these genes, thereby monopolizing the breast cancer diagnostic market. The Supreme Court’s decision relied on the statutory provisions in 35 U.S.C. § 101, which addresses patentable subject matter. The court has found exceptions to what is patentable, including laws of nature and natural phenomena. In terms of biological material, if the invention or process is something that naturally occurs, then it is ineligible for patent protection. 

Some eligible biological patents granted in the past include the PCR process and transgenic animals – an animal whose genome has been edited to contain genes from another species. The first transgenic mammal patented was the Harvard Oncomouse, developed by Harvard in the 1980s. This mouse was genetically modified to be more likely to develop cancerous tumors, making it a valuable cancer research subject, and patent eligible. 

Innovation for novel developments in the transplant space, like the genetically modified pig kidney, is encouraged by the patent protection of inventions utilized for xenotransplantation technology. eGenesis has received a number of patents related to the xenotransplantation process, including utility patents for the methods to generate genetically modified animals/cells and for genetically modified animals/tissue/cells used for xenotransplantation.  

The narrowing of biological patents to non-naturally occurring subject matter allows for companies like eGenesis to obtain patents for biological innovations while still protecting research and development efforts, particularly diagnostic testing of carrier genes. Patent eligibility of biological and natural phenomena is currently being addressed in Congress. On June 22, 2023, the US Senate released the Patent Eligibility Reform Act of 2023 (“PERA”). If passed, this act would clarify patent-eligible subject matter and potentially allow for the patenting of solely isolated genes, possibly overriding the Myriad decision. 

While patent eligibility of biological subject matter has the potential to allow for greater innovations, like modified organ transplants, expanding patent-eligible material may lead to negative downstream impacts. Granting monopolies can lead to access issues for diagnostic testing and increasing costs to use isolated genes in research and development efforts. Granting patent protection to biological patents is important and the right balance is necessary to further innovation and facilitate problem solving medical solutions. While patent law is complicated and evolving, novel advancements like the pig kidney transplant are largely driven by innovation incentives and a greater need for medical solutions to the transplant wait list issue.

Gene Editing and IP Battles: The Fight for CRISPR/Cas-9 Patent Rights

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Photo by Google DeepMind on Pexels.com

By: Bethany Butler

Gene editing technologies have the potential to greatly influence medicine and impact future therapies to treat debilitating conditions. Gene editing research seeks to “modify genes of living organisms to improve our understanding of gene function and develop ways to use it to treat genetic or acquired diseases.” One gene editing tool is the CRISPR/Cas-9 system, which allows for precision genome editing by cutting DNA in targeted locations for replacement. The first gene editing therapy utilizing CRISPR/Cas-9, called Casgevy, was approved by the Food and Drug Administration (FDA) in December of 2023. Casgevy is a treatment for patients with sickle cell disease, an inherited blood disorder that may cause painful symptoms and require lifelong interventions.

The emergence of CRISPR/Cas-9 Technology

The history of the CRISPR/Cas-9 system’s discovery and application largely involves two prominent research teams battling for its intellectual property rights. One team (“the Broad Institute”) hails from molecular biologist Feng Zhang of the Broad Institute, Harvard University, and the Massachusetts Institute of Technology; the other (“Charpentier and Doudna”) represents researcher Emmanuelle Charpentier of the Max Planck Institute for Infection Biology, Jennifer Doudna of the University of California, Berkeley, and the University of Vienna. Both teams have found success with their CRISPR/Cas-9 systems. In 2020, Emmanuelle Charpentier and Jennifer Doudna won the Nobel Prize in chemistry for the team’s 2012 discovery of the Cas-9 enzyme’s role in the CRISPR process. 

The two groups have not existed in harmony though, as patent battles between them stem from each groups’ 2012 US Patent and Trademark Office (“USPTO”) filings. Both teams filed applications to protect their respective gene editing tools, and unless the teams claimed distinct inventions regarding the use of the CRISPR/Cas-9 technology in human genomes, the USPTO would not allow patent protection to extend to both. 

Patent Protections of Gene Editing Technology

There are three types of patents that an inventor may file with the USPTO: utility, design, and plant. Gene editing technologies, like the CRISPR/Cas-9 system, often fall under the utility patent category. Utility patents are useful, new, and non-obvious. The non-obvious requirement refers to if a person of ordinary skill in the art would likely predict the invention by combining prior art references. CRISPR/Cas-9 patent rights come with limited monopolies, the potential for patent royalties, access to license the technology for future therapies in human cells, like the newly approved sickle cell therapy. 

Charpentier and Doudna’s May 2012 patent application demonstrated the use of this technology but did not go so far as to claim its use in eukaryotic cells (i.e. CRISPR/Cas-9 gene editing in human cells). Conversely, the Broad Institute demonstrated the use of this technology specifically in eukaryotic cells in their December 2012 patent application. The Broad Institute’s patent application was approved on April 15, 2014, and the team received the first patent for a method of altering eukaryotic cells using the technology. 

The CRISPR/Cas-9 Patent Fight

The Broad Institute, led by molecular biologist Feng Zhang, prevailed over Doudna and Charpentier regarding patent rights related to the CRISPR/Cas-9 technology. The main issue over these rights is which team developed the use of the CRISPR/Cas-9 gene editing in the modification of eukaryotic genomes.

Over the last 10 years, the two research teams have appealed various patent decisions, with the Patent Trials and Appeals Board (PTAB) and the Federal Circuit continually ruling in favor of the Broad Institute. For example, in a 2017 appeal, the Federal Circuit confirmed the PTAB’s finding that the Broad Institute’s claims were non-obvious regarding “the extent to which the art provided instructions for applying the CRISPRCas9 technology in a new environment”. The latest decision was on February 28, 2022, confirming the Broad Institute’s team was the first to invent the technology for modifying genomes in human cells. The decision stemmed from earlier interference claims holding that the Broad Institute’s patents claimed distinct subject matter compared to Doudna and Charpentier’s claims. Currently, the Broad Institute and Zhang’s team has prevailed in the patent space for the rights to CRISPR/Cas-9 gene editing technology in eukaryotic cells and now are able to license this technology for therapeutic applications. 

The CRISPR/Cas-9 Technology In Action Today

The Broad Institute licensed its technology to Editas Medicine in 2014. Vertex Pharmaceuticals, the pharmaceutical company that developed the sickle cell therapy, Casgevy, reached a licensing deal with Editas Medicine in December 2023. This deal pertains to the use of the CRISPR/Cas-9 technology in the Casgevy treatment and other sickle cell therapies. Individuals with sickle cell disease inherit genes that encode for abnormal hemoglobin production resulting in abnormal red blood cells. The Casgevy treatment uses the CRISPR/Cas-9 technology to edit patients’ blood stem cells to increase the production of fetal hemoglobin, which is not affected by the sickle cell mutation, thereby diluting the affected sickled blood cells. The edited cells are then infused back into the patient and have the potential to treat the disease. For the use of this technology, Vertex Pharmaceuticals agreed to pay Editas Medicine $50 million dollars upfront and licensing fees through 2034 ranging from $10 million to $40 million dollars annually. 

The far reaches of gene editing technologies have the potential to transform medicine and better the lives of many. CRISPR/Cas-9 editing technology is a vital therapeutic tool in this space and the fight for its patent rights continues. With the rollout of novel therapies, U.S. patent law is the key to lucrative licensing deals for the victors in these CRISPR/Cas-9 patent wars.