(May 25, 2022) SIGA Technologies Inc., a New York-based pharmaceutical company, has received approval from the U.S. Food and Drug Administration (FDA) for an intravenous formulation of TPOXX (tecovirimat) for the treatment of smallpox. The U.S., Canada, and Europe have approved an oral formulation for treating smallpox, and Europe has also approved it for treating monkeypox and cowpox. The newly approved intravenous formulation provides an option for patients who are unable to swallow.
The approval is welcome news as over 100 cases of monkeypox have been identified outside its endemic area. Australia, Belgium, France, the U.K., Sweden, Italy, Spain, Portugal, Canada, and the United States have reported cases. The World Health Organization (WHO) warns more cases are likely.
Monkeypox is endemic to Central and West Africa and belongs to a subset of the Poxviridae virus family, which includes smallpox and cowpox. Monkeypox symptoms (fever, sweating, headaches, enlarged lymph nodes) are generally much milder than smallpox. The infection generally spreads from animal to human. However, it can also be transmitted between humans. This can occur through contact with bodily fluids, lesions on the skin or on internal mucosal surfaces, such as in the mouth or throat, respiratory droplets, and contaminated objects.
TPOXX is the first antipoxviral drug approved in the United States.
On May 13, 2022, Medtronic, Inc. announced that it completed the acquisition of Intersect ENT, Inc. The transaction was only able to gain approval of the Federal Trade Commission (FTC) upon the agreement that Medtronic sell the assets of Fiagon NA Corp., a key subsidiary of Intersect ENT. Medtronic sold Fiagon to Hemostasis LLC and was thereupon able to finalize the acquisition of Intersect ENT.
As a result of the transaction, Medtronic acquired Intersect ENT’s PROPEL™ and SINUVA™ (mometasone furoate) sinus implant product lines and technology, intellectual property, and Intersect ENT’s facility in Menlo Park, CA. Intersect ENT employees joined Medtronic as a result of the acquisition.
SINUVA is an FDA-approved biosorbable, steroid-eluting implant that, according to Intersect ENT, is clinically proven to reduce polyps and symptoms of nasal congestion. PROPEL is also an FDA-approved biosorbable, steroid-eluting implant, indicated for patients with chronic rhinosinusitis (CRS). The PROPEL implant, which has reportedly also received CE mark clearance in Europe, is designed to keep sinuses clear after an endoscopic sinus procedure, while the SINUVA device is inserted to treat nasal polyps that develop after ethmoid sinus surgery.
Medtronic reports that acquiring Intersect ENT’s product lines and customer base will further Medtronic’s efforts to help patients who suffer from chronic rhinosinusitis, reported to be one of the most common health care problems in the U.S.
The FTC’s Bureau of Competition investigated the planned acquisition of Intersect ENT and determined that Medtronic, Inc., a wholly owned subsidiary of Medtronic plc, and Intersect ENT violated Section 7 of the Clayton Act, as amended, 15 U.S.C. § 18, and Section 5 of the Federal Trade Commission Act, as amended, 15 U.S.C. § 45.
An agreement was reached between Medtronic, Intersect ENT, and the FTC, pursuant to which Fiagon was sold to Hemostasis LLC.
Fiagon makes ear, nose, and throat navigation systems and balloon sinus dilation products. According to the draft Complaint prepared by the FTC, without this divestiture, the acquisition of Intersect ENT by Medtronic would pose a threat to future competition in the United States for both ENT navigation systems and balloon sinus dilation products.
The press release by Medtronic is available here.
On May 5, 2022, the FDA’s Center for Devices and Radiological Health (CDRH) issued draft guidance regarding the FDA’s Voluntary Improvement Program (“VIP”). The draft guidance, Fostering Medical Device Improvement: FDA Activities and Engagement with the Voluntary Improvement Program, can be found here. According to the FDA:
“The VIP is a voluntary program facilitated through the Medical Device Innovation Consortium (MDIC) that evaluates the capability and performance of a medical device manufacturer’s practices using third-party appraisals, and is intended to guide improvement to enhance the quality of devices.”
The VIP draft guidance, is an extension of the 2018 pilot program Case for Quality Voluntary Medical Device Manufacturing and Product Quality (“CfQ Pilot Program”). According to the FDA, the CfQ Pilot Program assessed the “capability and performance of key business processes using a series of integrated best practices detailed in the Information Systems Audit and Control Association (ISACA) Capability Maturity Model Integration (CMMI) system.” The results of the pilot program can be found here. Participants in the CfQ Pilot Program reported that “the appraisal had a direct value to product quality and over 90% reported a positive experience with the appraisal.”
As described in the draft guidance, the goal of the VIP is to “elevate and enhance manufacturing practices and behaviors through which quality and safety of medical devices can be improved.” As indicated in its name, this program is voluntary. Through use of the program, third-party appraisers visit participants to evaluate their practices in order to identify strengths and areas for improvement.
According to the draft guidance, VIP offers various benefits and opportunities for those manufacturing sites who demonstrate sustained capability and performance. Examples of opportunities from the draft guidance include:
- FDA Consideration in Risk-Based Inspection Planning
- Utilization of a Modified Submission Format for Premarket Approval Application (PMA) and Humanitarian Device Exemption (HDE) 30-Day Change Notices for Modifications to Manufacturing Procedures or Methods of Manufacture
- Utilization of a Modified Submission Format for PMA and HDE Manufacturing Site Change Supplements
- Utilization of a Modified Submission Format for PMA or HDE – Manufacturing Modules
The VIP has various participation and enrollment criteria for manufacturing sites, which can be found here.
The FDA requests comments on the draft guidance by July 5, 2022.
On April 08, 2022, the Food and Drug Administration (FDA) published a draft cybersecurity guidance document for medical devices, titled Cybersecurity in Medical Devices: Quality System Considerations and Content of Premarket Submissions. The draft guidance covers a wide range of issues, including cybersecurity device design, labeling, and documentation. The guidance is intended to provide medical device makers a road map on how to satisfy the FDA’s quality system and patient safety regulations and how to address cybersecurity considerations within their premarket submissions.
The FDA’s draft guidance was released shortly before a report underlining the cybersecurity security practice deficiencies of various medical device makers. On April 20, 2022, Cybellum – a company specializing in assessing product security – reported the results of its 2022 medical device cybersecurity survey in an article titled Medical Device Cybersecurity: Trends and Predictions. The survey found that, although 83% of the medical device companies surveyed saw device security as a competitive edge, 75% of respondents noted that they do not have a dedicated senior management who takes responsibility for device cybersecurity.
The Cybellum survey also revealed that only about a quarter of the medical device companies surveyed (27%) generate and maintain a Software Bill-of-Materials (SBoM) for their products. An SBoM is a formal record containing the details and supply chain relationships of various components used in building software. President Joe Biden previously highlighted the importance of an SBoM in his Executive Order on Improving the Nation’s Cybersecurity from May 2021. Moreover, the National Telecommunications and Information Administration published The Minimum Elements for an SBoM on July 21, 2021, in an effort to bring “transparency to the components and connections within and across supply chains.”
The FDA’s draft cybersecurity guidance document is available here and is available for stakeholder comments until July 7, 2022.
ResApp Health recently announced its planned sale to Pfizer Australia, a wholly owned subsidiary of Pfizer Inc. Pfizer agrees it would acquire 100% of the shares for AUD $0.115 / share, for a total equity value of approximately AUD $100 million. ResApp directors announced a unanimous recommendation to sell, and their intent to vote their own shares accordingly. A shareholder vote is scheduled for June.
ResApp Health develops point of care diagnostics for telehealth that integrate with existing platforms. Their algorithms can diagnose disease from sounds. For example, one platform reportedly diagnoses respiratory problems based on the sound of a patient’s cough or breathing, and no physical contact is required.
The companies will also enter a Research & Development License Agreement to collaborate on products in the field of COVID-19.
In a statement, Pfizer Australia’s Lidia Fonseca stated that “this proposed acquisition and research collaboration add to our growing digital capabilities and bolster our efforts to pave a new era for digital health.” ResApp CEO Tony Keating expressed excitement, stating “the material premium and certainty of an all cash consideration is an attractive outcome for our shareholders.”
This acquisition would be the second for Pfizer this year. Earlier, it acquired ReViral, the developer of therapeutics for respiratory viruses, for $525 million.
Cybellum released a medical device survey report on April 20, 2022 entitled “Medical Device Cybersecurity: Trends and Predictions.” The company’s website states that their “mission is to enable manufacturers and their suppliers to develop and maintain products that aren’t just safe, but are also secure.”
According to the company website, in preparing the new report, Cybellum “asked top security experts from hundreds of medical device manufacturers, about their main challenges and how they plan to solve them in 2022, and beyond.”
Cybellum lists the following key findings from the report:
Almost 90% admitted they need to improve on key areas, such as SBOM [software bill of materials] analysis and compliance readiness
Over 55% do not have a dedicated response team (PSIRT) in place
Almost 55% increased their cybersecurity budget by more than 25% in 2022
Other media outlets described the report as finding “widespread cybersecurity noncompliance despite rising investment,” and “[m]ore than half of medical device companies think they are noncompliant with cybersecurity regulations, standards and guidelines.” Further, “compliance with requirements ranged from 54% for Food and Drug Administration premarket submissions to 37% for International Medical Device Regulators Forum (IMDRF) cybersecurity principles and practices.”
According to MedTechDive, the report states that “[m]ore than 80% of respondents see device security as a competitive advantage and almost every polled company increased its security budget this year. However, 78% of those surveyed indicated they are doing the minimum to achieve compliance and 80% view device security as a ‘necessary evil’ imposed by regulators.”
According to a press release by Cybellum, “[m]edical device cybersecurity has become an extremely complex challenge. With medical devices becoming software-driven machines, and the rapid pace at which cybersecurity risk evolves due to new vulnerabilities, complex supply chains, new suppliers, and new product lines, it has become seemingly impossible to keep the entire product portfolio secure and compliant at all times. It is now more important than ever to learn from peers and try to find the best way forward.”
The full text of the survey report can be found here.
On April 11, 2022, Niazi Licensing Corporation (“Niazi”) succeeded in part in its appeal at the Federal Circuit in Niazi Licensing Corporation v. St. Jude Medical S.C. Inc. Niazi’s lawsuit alleged that St. Jude Medical S.C. Inc.’s (“St. Jude”) CPS telescoping catheter system infringed U.S. Patent No. 6,638,268, entitled “Catheter to Cannulate the Coronary Sinus” (the “‘268 patent”).
The district court determined that the terms “resilient” and “pliable” in the claims rendered all but one claim of the ‘268 patent indefinite and, therefore, invalid. However, the Federal Circuit reversed the district court’s holding and instead found that, although the terms may be broad, they are not uncertain. The Federal Circuit held that intrinsic record and extrinsic evidence are sufficient to inform a skilled artisan of the meanings of the terms with reasonable certainty. The court sent the case back to the district court to resolve any outstanding questions of whether St. Jude infringed the claims and whether St. Jude’s remaining invalidity defenses are applicable.
The Federal Circuit’s complete decision is available here.
Becton Dickinson’s PureWick Wins Patent Infringement Suit Against Stryker’s Sage Products Related To Female External Catheters
PureWick Corp., a Becton Dickinson company, succeeded in its infringement lawsuit PureWick Corp. v. Sage Products LLC. PureWick’s lawsuit alleged that Sage Products infringed U.S. Patent Nos. 10,226,376; 10,390,989; 10,376,407, which relate to a female external catheter that purports to reduce catheter-associated infections and other issues with traditional medical equipment.
The Delaware jury determined that Sage Products, a Stryker company, infringed all of PureWick’s claims with its competing product, and rejected Sage’s non-infringement and invalidity counterclaims. The jury awarded PureWick $26.2 million in lost profits resulting from the infringement, and $1.8 million as a royalty for Sage Products’ sale of the infringing product. The jury also determined that Sage Products willfully infringed two of the three patents.
(Mar. 31, 2022) Last Friday, ImmunoGen won an appeal at the Federal Circuit in ImmunoGen, Inc. v. Hirshfeld. The lawsuit is a civil action to order the granting of U.S. Application No. 14/509,809 (‘809), titled “Anti-FOLR Immunoconjugate Dosing Regimens”:
A federal judge in Virginia ruled it unpatentable, but the Federal Circuit overturned that decision.
The ‘809 application relates to dosing for the cancer drug mirvetuximab, an immunoconjugate. Generally, immunoconjugates include (1) an antibody portion typically targeting a cell of interest, and (2) a drug coupled to the antibody through a chemical linker. The antibody portion of mirvetuximab targets a folate receptor often overexpressed in ovarian and peritoneal cancer cells.
Early clinical trials for mirvetuximab were mixed. The drug was effective, but caused ocular toxicity if dosage exceeded a certain threshold. The ‘809 application claimed dosing below this threshold: “a dose of 6 milligrams (mg) per kilogram (kg) of adjusted ideal body weight (AIBW) of the patient.” AIBW accounts for a patient’s sex, total body weight, and height.
The district court had ruled on summary judgment that the ‘809 application was indefinite and obvious. However, the Federal Circuit held this violated proper procedure by resolving factual disputes against ImmunoGen, the non-moving party.
In one such dispute, the district court had found the ‘809 application indefinite partly because “for example” preceded the AIBW formula in the specification. It held this example did not fall within the claims and declined to hear expert testimony regarding whether a skilled artisan would use the formula. But the Federal Circuit pointed to a particular claimed dosing regimen for a specific immunoconjugate, reasoning this could lead one of skill in the art to choose a specific corresponding AIBW formula. This undermined the district court’s finding of indefiniteness.
In another factual dispute, the district court had held the claims obvious because based on prior art, a skilled artisan would have known to use AIBW dosing to address mirvetuximab’s side effects. The district court found ocular toxicity was a known side effect of immunoconjugates, even though there was no directly supportive expert testimony. The Federal Circuit pointed to contrary evidence in the record: that side effects were not well understood and that it is difficult to generalize the pharmacological effects of immunoconjugates.
Accordingly, the Federal Circuit overturned the indefiniteness and obviousness findings and sent the case back to the district court. Now ImmunoGen has another opportunity to pursue grant of the ‘809 application.
Rasmussen Instruments, LLC (“Rasmussen”) won a $20M jury verdict against DePuy Synthes (“Depuy”), a part of Johnson & Johnson Medical Devices Companies. Rasmussen asserted Patent Nos. US 9,492,180 (‘180 patent) and US 10,517,583 (‘583 patent), both titled “Arthroplasty systems and methods for optimally aligning and tensioning a knee prosthesis,” against DePuy’s “Balanced Sizer” product for its Attune® Knee System.
According to the complaint filed in 2020, Dr. G. Lynn Rasmussen is an orthopedic surgeon based in Murray, Utah, with over 40 years of experience in reconstructive orthopedic surgery and is the sole member and owner of Rasmussen. Both the ‘180 patent and ‘583 patent claim priority to a provisional application filed in 2005 by Dr. Rasmussen. The complaint alleges that the ‘180 patent and ‘583 patent “describe and claim . . . a device for maintaining the tension in the ligaments of a knee joint and/or adjusting the alignment of a knee joint during knee replacement surgery.”
According to the complaint, from 2012 to 2014, Dr. Rasmussen discussed licensing the patented technology with DePuy, but after the negotiations broke down, Rasmussen initiated litigation against DePuy. After a trial in March of 2022, the jury decided that DePuy’s “Balanced Sizer” product infringed the ‘180 patent but did not infringe the ‘583 patent. The jury also decided that DePuy’s infringement of the ‘183 patent was willful and that Rasmussen’s damages were therefore $20 million. The jury also held that the ‘180 patent and the ‘583 patent were not invalid.
The case is No. 1:20-CV-11807-WGY in the U.S. District Court for the District of Massachusetts, Eastern Division.
Find additional information and resources for the medical device community at Knobbe Medical.