The U.S. Patent and Trademark Office (“USPTO”) quietly increased the examiners’ arsenal by slipping a new rejection into the latest revision of the Manual of Patent Examining Procedure (“MPEP”) released last month. One of the changes made in this revision is the addition of a new “improper Markush grouping” section, MPEP § 706.03(y), which authorizes patent examiners to reject a claim on the basis that it contains an improper listing of alternative elements. Patent applications in the life sciences, which frequently have claims in the “Markush” format, may soon face the new “improper Markush grouping” rejections.
A “Markush” claim format is often used as a straightforward way to capture various alternatives for a given element in a single claim. It is named after the patent applicant (Eugene A. Markush) who used this format in a court case that was decided in 1924. Markush claims contain a customized list of elements that are useful for the purposes of the claim. As an example, for the purposes of describing various alternative materials to coat an implant screw, a claim could contain a list such as “ceramic, glass, plastic, or metal.”
Prior to the recent MPEP revision, improper Markush grouping rejections had been uncommon because they were based on guidelines issued by the USPTO in 2011. However, now that the new section has been added to the MPEP, it is expected that rejections of patent applications based on improper Markush grouping will become much more frequent. The examiner can now make a rejection based on improper Markush grouping if the examiner determines that the members of a Markush group lack either a single structural similarity or a common use, or if the single structural similarity is a substantial structural feature of a chemical compound that is not essential to the common use. As to timing, the examiner should make a rejection based on an improper Markush grouping in the first action on the merits after presentation of the claim with the allegedly improper Markush grouping.
When making the improper Markush grouping rejection, the new MPEP section instructs the examiner to include suggestions for the applicant as to how to overcome the rejection, e.g., by suggesting a proper Markush grouping based on the specification as filed and/or by suggesting that applicant set forth each alternative (or grouping of patentably indistinct alternatives) within an allegedly improper Markush grouping in a series of independent or dependent claims. In doing so, the examiner cannot suggest any grouping that clearly would not meet the requirements of 35 U.S.C. § 112(a). For example, the examiner should not suggest a grouping that meets the requirements for a proper Markush grouping, but which would clearly lack adequate written description if presented in a separate claim.
The new MPEP section states that an improper Markush grouping rejection can be overcome by (1) amending the rejected claim such that the Markush grouping includes only members that share a single structural similarity and a common use; or (2) by presenting convincing arguments why the members of the Markush grouping share a single structural similarity and common use (i.e., are members of a physical, chemical, or art-recognized class that share a common use, or are chemical compounds that share a substantial structural feature that is essential to the common use).
In addition, even if the applicant does not take action sufficient to overcome the improper Markush grouping rejection, when all of the claims are otherwise in condition for allowance the examiner is instructed to reconsider the propriety of the improper Markush grouping rejection. If the examiner determines that in light of the prior art and the record as a whole the alternatives of the Markush grouping share a single structural similarity and a common use, then the rejection should be withdrawn. Note that no Markush claim can be allowed until any improper Markush grouping rejection has been overcome or withdrawn, and all other conditions of patentability have been satisfied.
The USPTO, by introducing section 706.03(y) into the MPEP, has taken the position that improper Markush grouping is a rejection on the merits and can be appealed to the PTAB. When drafting a Markush claim, patent practitioners should keep this new MPEP section in mind and recite members of the Markush grouping that share a single structural similarity and common use.
Xeris Pharmaceuticals, Inc. (“Xeris”) recently announced successful completion of both adult and pediatric clinical studies for its glucagon rescue pen. According to Xeris’ President and CEO Paul Edick:
Xeris is on-track to submit an NDA for our ready-to-use glucagon rescue pen for the treatment of severe hypoglycemia in late Q2 of this year. We will use the data from the Phase 3b study to gain additional information regarding the entire treatment episode, including preparation and administration time of the current glucagon emergency kits versus our rescue pen auto-injector, for people with diabetes who may require glucagon in emergency situations.
Xeris also recently released results from a Human Factors usability and reliability study which, according to Xeris, demonstrated a 99% success rate for patients in administering full doses of glucagon with the rescue pen using a simple 2-step process.
Xeris notes that glucagon treatment is critical for persons susceptible to severe hypoglycemic events. Severe hypoglycemia, if untreated, can result in seizures, coma, brain damage, and if left unaddressed, even death. Along with insulin, glucagon helps maintain the glycemic control system which in turn keeps blood glucose at optimum levels within the body. The American Diabetes Association recommends glucagon be prescribed for persons facing increased risks of hypoglycemia. According to Xeris, due to limitations in current glucagon products and the difficulty involved in administration methods (especially in emergency situations), such treatments have been underutilized by persons at risk of suffering from severe hypoglycemic events.
According to Xeris, their rescue pen aims to provide ready-to-use, room-temperature stable, and injectable and infusible drug formulations. Xeris’ proprietary XeriSolTM and XeriJectTM formulations are currently being examined for administration in both subcutaneous and intramuscular delivery sites. Xeris states that unlike some injectable drug formulations provided as a powder that is later reconstituted with water at the time of administration, Xeris’ formulations are non-aqueous, ultra-concentrated and ultra-low volume, biocompatible solutions or pastes. Xeris also reports that their formulations are packaged in a ready-to-use compatible syringe, such as its rescue pen auto-injector, or other compatible devices, such as vials, pens, or pumps.
U.S. to Have its Own Supply of the Most Commonly Used Medical Imaging Isotope for the First Time in 30 Years
Medical imaging isotopes are used to diagnose various diseases, such as cancer and coronary artery disease, and to evaluate brain, lung, kidney, and liver function. According to an U.S. Food and Drug Administration (FDA) press release, the most widely used medical imaging isotope, Technetium-99m (Tc-99m), is used in over 80% of the United States’ nuclear medical imaging procedures. Used in conjunction with certain diagnostic scanner devices, Tc-99m transmits signals which are used to generate images of organs. This information assists medical professionals in detecting medical issues and making decisions related to diagnosis and treatment.
According to Janet Woodcock, M.D., director of the FDA’s Center for Drug Evaluation and Research, “[e]very day, tens of thousands of people in the U.S. undergo a nuclear medical imaging procedure that depends on Tc-99m.” However, according to the FDA press release, for thirty years, the U.S. has relied on other countries for its supply of Molybdenum-99 (Mo-99), the source of Tc-99m. As part of that process, the U.S. has been exporting highly enriched uranium. As a result of the complex supply chain, the U.S. has encountered challenges such as high costs and shortages of the isotope. Supply chain issues have also caused many medical professionals to opt to use different isotopes, which can mean higher doses of radiation or even higher costs.
To try to remedy some of these issues, Congress enacted the American Medical Isotopes Production Act in 2012. According to the FDA press release, the act required evaluation of and support for projects related to the domestic production of Mo-99 for medical purposes, without the use of highly enriched uranium.
The FDA press release notes that the U.S. Food and Drug Administration (FDA) has now approved NorthStar Medical Radioisotopes’ RadioGenix System, which is the first system for producing Tc-99m that uses non-uranium based Mo-99. According to Dr. Woodcock, the FDA’s approval of this system “will help to ensure more reliable, clean and secure access to this important imaging agent…”
According to a statement by FDA Commissioner Scott Gottlieb, M.D.,
while we needed to preserve the availability of Tc-99m for its important medical purpose, it was critical that we find a more stable, secure and sustainable technology for production.
Moving forward, according to the FDA announcement, the Nuclear Regulatory Commission is “issuing guidance that will advise medical and commercial nuclear pharmacy users on the license amendments they will need to possess and use the RadioGenix System.”
The FDA recently cleared Prescient Surgical’s CleanCisionTM Wound Retraction and Protection System (CleanCisionTM), a retractable device designed to prevent surgical site infection. According to Prescient Surgical, CleanCisionTM is “a novel, first-in-class, advanced intraoperative infection control system” that utilizes an active cleansing technology.
Traditionally, practices for preventing surgical site infections (SSIs) involve administering drugs, controlling patient’s blood glucose level, maintaining optimal temperature and tissue oxygenation, using skin prep agents, and using plastic wound protectors.
The press release states that unlike traditional methods, ClearCision combines wound protection and wound cleansing. Retractable plastic sleeves protect the wound while providing direct access to the surgical site. Irrigation system continuously cleans the wound edge using sterile irrigant solution and removes contaminant using suction. Insoo Suh, cofounder of Prescient Surgical, noted that ClearCision is “a proactive approach to clearing contamination during surgery.”
The press release also notes that SSIs can be caused by bacteria entering the surgical incision site, and lead to significant financial burdens on teh healthcare system.
Jonathan Coe, cofounder, president, and CEO of Prescient Surgical, said in the press release that the company is “initially focusing on abdominal surgery and particularly colorectal surgery, where the risk, frequency and severity of [SSI] is high and the need is acute.”
The Food and Drug Administration recently announced approval of the RadioGenix™ System, a technetium 99m (Tc-99m) generator. The RadioGenix™ System is developed by NorthStar Medical Radioisotopes, LLC, a nuclear medicine technology company.
According to the press release, Tc-99m is a diagnostic agent used in more than 40,000 imaging procedures daily for diagnosis and treatment of patients. Prior to approval of the RadioGenix™ System, Tc-99m could only be produced from enriched uranium in facilities outside of the United States that relied on a complicated and potentially unreliable supply of stable uranium radioisotopes. The development of the RadioGenix™ System alleviates these vulnerabilities by providing a reliable domestic source of Tc-99m.
This radioisotope is vital to disease detection, yet health care professionals have faced challenges with adequate supply due to a complex supply chain that sometimes resulted in shortages. Today’s approval has been the result of years of coordination across the FDA and with U.S. government organizations and marks the first domestic supply of Mo-99 – the source of Tc-99m – in 30 years, which will help to ensure more reliable, clean and secure access to this important imaging agent used in nuclear medicine.
According to NorthStar, the RadioGenix™ System is the first and only device for producing a non-uranium Tc-99m. Rather than uranium, the system uses molybdenite, a naturally occurring molybdenum found in the earth’s crust, as the starting material. Major applications of Tc-99m include detection of potential diseases like coronary artery disease and cancer, as well as evaluating lung, liver, kidney, and brain function.
The FDA has recently approved Embrace, a smart watch designed to monitor epileptic patients for seizures, according to a press release. According to the press release, the device uses machine learning to monitor patients for dangerous seizures, including grand mal or generalized tonic-clonic seizures. These seizures cause loss of consciousness and can cause a state of confusion in patients for periods of time after they finish. Embrace is said to allow medical professionals to gain information about when seizures happen with higher accuracy than was previously available and can also alert caregivers when patients are having seizures. During a seizure, the watch vibrates, LEDs light up, and an alert is sent via Bluetooth to the patient’s smartphone. An app on the phone can then send a distress signal via text or phone call to one or more caregivers.
The device was previously approved by the European Medical Agency in April 2017. According to articles, the technology was originally developed at MIT in 2007 and was funded by a successful crowdfunding campaign in 2014, which netted the maker, Empatica, more than $800,000. Embrace went on sale shortly after that campaign and has been available commercially but was not previously available as a medical device in the U.S.
The FDA’s approval was reportedly based on a clinical trial of 135 patients over 272 days. Each of the patients had epilepsy and were simultaneously monitored by EEG and using Embrace. The trial recorded over 6500 hours of data, including 40 seizures, which Embrace detected with 100% accuracy.
Matteo Lai, Co-Founder and CEO of Empatica, touted Embrace’s design and functionality, saying “We wanted to design the world’s first medical device that could win a design award, while being used as a lifesaving product.” Embrace is said to be the first smart watch to be approved by the FDA for neurological monitoring.
On January 31, 2018, the European Commission adopted a legislative proposal with the aim of strengthening EU cooperation among Member States when conducting a Health Technology Assessment (HTA) of new medicines and certain new medical devices. The European Commission Fact Sheet explains that HTA is a procedure for assessing the added value of new medicines and medical devices, for example, assessing whether a new scanner will lead to a better diagnosis or whether a new surgery will improve the patient’s treatment.
BEUC, the European Consumer Organization, explained in a press release that at the moment, around 50 national and regional HTA authorities provide Member States with clinical data, however, work carried out by one authority is often replicated by another, leading to inefficiency in EU health systems.
The Commission’s proposal establishes four areas of joint work between Member States at EU-level:
- Joint clinical assessments focusing on the most innovative health technologies with the most potential impact for patients;
- Joint scientific consultations, or “early dialogue,” whereby developers can seek advice from HTA authorities;
- Identification of emerging health technologies, commonly referred to as ‘horizon scanning’, to identify promising technologies early; and
- Voluntary cooperation on other areas.
In a press release, the Commission added that “manufacturers will no longer have to adapt to different national procedures.” Not all work will be done jointly, the Commission’s press release indicates that individual EU countries will continue to be responsible for assessing non-clinical (e.g. economic, social, ethical) aspects of health technology, and making decisions on pricing and reimbursement. Thus, device manufacturers will still need to work with each Member State to determine pricing and reimbursement.
The Commission’s Q&A on the proposal explains that the joint clinical assessments will not affect market approval as they will only occur after the medical devices have obtained a CE mark. The Q&A also notes that HTA does not interfere with the conformity assessments of medical devices.
The Commission asserted in the Q&A that those benefiting from cooperation would include:
- Patients, who may benefit from a faster uptake of promising innovative technologies;
- Member States, whose national authorities will be able to pool their expertise and avoid duplication of efforts on clinical assessments, making better use of human and financial resources; and
- Industry, including SMEs, who will benefit from clearer rules and greater predictability for their business planning, and cost savings.
In a statement to EURACTIV.com, Yannis Natsis, Policy Manager for the European Public Health Association, cautioned:
A European approach must improve on the current system and deliver meaningful innovation and affordable treatments. There must not be the slightest doubt that cooperation would weaken it or make the assessments less rigorous.
A timeline proposed by the Commission indicates that the proposal could be adopted by the European Parliament and the Council of Ministers in 2019, become applicable three years later, and then have a further three-year transitional period to allow for Member States to phase-in the new system. The Q&A provides an example of a phase-in, suggesting the system could perform 10 to 15 joint clinical assessments in the first year of operation and reach around 65 assessments towards the end of the transitional period. The changes will likely happen after Britain has exited the European Union.
District Court Awarded Ultrasound Device Maker Verasonics $5.6 Million And World-Wide Injunction In Trade Secret Case
The United States District Court of Western District of Washington entered a judgment in a trade secret case, Verasonics, Inc. v. Alpinion Medical Systems Co., Ltd. (Case No. 2:14-cv-01820-JCC). The district court confirmed the final arbitration award, giving Plaintiff Verasonics, Inc. $5.6 million in damages, including fees and costs, and enjoining Defendant Alpinion Medical Systems Co., Ltd. from using Verasonics’ trade secret, including marketing or selling any devices using the trade secret for five years.
Verasonics, Inc. describes itself as a Kirkland, Washington-based company that specializes in ultrasound devices and technology. In the complaint filed on November 26, 2014, Verasonics alleged that Alpinion, headquartered in Seoul, South Korea, showed interest in “licensing, co-development or investment” opportunities with Verasonics starting from 2010. Alpinion allegedly “induced” Verasonics into revealing its trade secrets and confidential information to Alpinion as the two parties entered into a series of Non-Disclosure Agreements (“NDAs”), and lease agreements for Alpinion to lease two research ultrasound systems from Verasonics. The complaint also alleged that Alpinion made a below-market offer to Verasonics, which was rejected, and that Alpinion represented that its interest was in commercial ultrasound products, not in research ultrasound devices.
However, Alpinion later announced its own eCube-12R ultrasound platform specifically designed for the research market. Verasonics sued Alpinion for trade secret misappropriation under the Washington State Uniform Trade Secret Act in addition to breach of contract claims in the Western District of Washington.
In 2015, the case at the district court was stayed pending a binding arbitration at the American Arbitration Association (case name ICDR No. 01-15-0002-9484). The arbitrator found that Alpinion breached the parties’ NDAs and lease agreement, and violoated the Washington Uniform Trade Secret Act. The arbitrator issued a partial final arbitration award of $2.9 million in compensatory damages and a five-year injunction against Alpinion on March 2, 2017. The partial arbitration award was filed under seal and not publicly available. According to Davis Wright Tremaine LLP, the law firm representing Verasonics in this matter, the injunction against marketing and sales of the accused product is worldwide. The arbitrator subsequently issued a final award on June 26, 2017, ordering Alpinion to pay Verasonics another $2.7 million in attorneys’ and arbitration fees and other expenses.
According to a press release made after the partial final award, Lauren Pflugrath, president and CEO of Verasonics, said:
We are grateful for the arbitrator’s decision to issue the Final Award so clearly in our favor. We continue to expand and build positive collaborative partnerships, but must insist on protecting our intellectual property.
Wright Medical Group recently announced the acquisition of IMASCAP SAS for $88 million. According to the press release, Wright Medical Group (NASDAQ: WMGI) is a publicly traded company focusing on extremity joint replacement and bio-orthopedic material development. IMASCAP SAS focuses on developing software for preoperative joint replacement surgery.
According to the press release, the companies have had a previous relationship where Wright Medical Group used IMASCAP’s Genosys technology in its BLUEPRINT 3D planning software. The technology is said to allow surgeons to visualize potential movement in a shoulder joint so as to determine the best type of implant to use. The program is reported to use data provided entirely from a computed tomography scan. The press release notes that using the program allows surgeons to save time during surgery by adjusting their strategy beforehand. Since Genosys’s release in 2014, the company lists its use in 3800 pre-operative planning procedures, by over 1000 surgeons, in 21 countries .
The press release notes that the deal includes approximately $46.9 million in cash, $15.6 million in ordinary shares, and approximately $26.3 million, in potential earnouts and milestone payments for new software and implant systems.
In the press release, Robert Palmisano, President and Chief Executive Officer of Wright Medical Group, stated, “Software-enhanced solutions are the future, and with the acquisition of IMASCAP, we have the opportunity to take a significant lead in this area”.
In a statement by IMASCAP’s Jean Chaoui, President and Chief Executive Officer, “We believe that Wright, with its global leadership position in the extremities market and expertise in medical education and product development, is the ideal partner to realize the full potential of IMASCAP’s technology and product pipeline”.
In its press release, Wright Medical Group also expressed interest in a variety of other technologies under development that could potentially help the company expand into other joint replacement areas. Currently, the company has plans to offer the software free of cost to physicians currently using its shoulder joint replacement technology.
BioArctic Announces Patent Allowance Entitled Spinal Cord Devices and Methods for Promoting Axonal Regeneration
BioArctic AB, a public Swedish biopharma company, recently announced that they received allowance of a patent application directed to a method of promoting axonal regeneration using a biodegradable spinal cord device. The medical device is said to be a component of BioArctic’s SC0806 product for treatment of complete spinal cord injury. The allowed claims are directed toward “selecting a spinal cord device” having certain geometric characteristics, “positioning peripheral autologous nerves in … through channels,” and implanting the device in an injured spinal cord. The device is said to be soakable in a solution of FGF1 growth factor prior to implantation. BioArctic reports to have received corresponding patents in China and Australia.
According to BioArctic, despite considerable research into bridging spinal cord gaps, no product is yet available on the market. BioArctic states that the SC0806 spinal cord product is currently undergoing Phase 1/2 clinical trials in Sweden and was granted orphan drug status in the European Union and the United States, qualifying the product for 10 and 7 years of market exclusivity, respectively. The product received funding from the European Union’s Horizon 2020 Research and Innovation Program, the EU’s largest public investment program for research and innovation, comprising an €80 billon investment over 7 years, culminating in 2020.
According to BioArctic, in addition to developing treatments for complete spinal cord injury, its research focuses on disease modifying treatments and reliable biomarkers and diagnostics for neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease, for which AbbVie has agreed to develop and commercialize BioArctic’s Parkinson’s antibody portfolio. European Biotechnology rated BioArctic’s €71.8 million IPO as one of Europe’s most successful in 2017.