Newsletter
New Medical Technology Series (1) — An Overview of BNCT Patent Development
In the field of medical radiation physics, significant advances in recent years have occurred in radiation methods and tumor localization. To achieve improved dose concentration, new radiation techniques have been developed, such as the use of radiation sources with improved physical properties, while more precise tumor localization allows more accuracy in positioning of target electrodes for irradiation.
Radiation therapy techniques using beams of photons or electrons have seen significant improvements due to increases in beam energy and radiation penetration. However, such increases in radiation-beam intensity, while successful at killing tumor cells, bring corresponding increases in damage to normal tissues as well.
In order to reduce radiation damage to healthy tissues surrounding tumors, principles drawn from chemotherapy, such as improved target identification, are being applied to radiotherapy. In addition, therapies using radiation sources with high relative biological effectiveness (RBE), such as proton therapy, heavy particle therapy and neutron capture therapy, are increasingly applied for treatment of tumor cells that have developed radioresistance. Combining the above two concepts, boron neutron capture therapy (BNCT) takes advantage of the specific agglomeration feature of a Boron-10 (10B)-containing drug in tumor cells together with the precision of neutron beam modulation to provide a therapeutic effect with less radiation damage.
How BNCT works
BNCT is based on the principle that the probability of thermal neutrons (generally referring to neutrons with energy below 1 eV) being captured in an environment with 10B drugs is much higher than that without 10B drugs. Therefore, when a 10B-containing drug is administered in sufficient concentration to tumor cells, most of the thermal neutrons irradiated on the tumor cells will react with the 10B-containing drug, causing rapid release of high-energy lithium-7 (7Li) and alpha particles (4He).
Since the maximum travel distance (range) of alpha particles is 8 μm and that of 7Li is 5 μm, equivalent to the size of a cell, and the linear energy transfer between the two particles' nuclei is above 150 keV/μm, the radiation damage can be limited to tumor cells with 10B-containing drugs, while normal tissue cells, which are at greater distances and which have not been dosed with 10B-containing drugs, suffer relatively little damage.
Geographical Factors and Patents Concerning the Technological Development of Medical Radiation Physics Technology
As the development and application of medical radiation physics do not occur in only a single country or region, geographical factors in such developments are inevitably subject to the fact that the patent system is based on territorial principles. Therefore, relevant patent portfolio strategies should be considered with regard to matters such as the countries or regions in which patents should be applied for, how patent applications for different countries should differ, and the patentabilities of various subjects.
Following are the key technical aspects of BNCT-related technology:
(1) Devices
1. Beam system: In Taiwan, cancer treatment via neutron beams is provided by the Tsinghua Open-pool Reactor (THOR), which generates neutron beams as a therapeutic beam source for medical and academic institutions with access to BNCT for cancer treatment and related research. An exemplary patent application for this subject matter is CN217119151U, “a four-treatment-room BNCT cancer treatment device based on aN INTENSE BEAM cyclotron."
2. Beam shaping assembly: The beam shaping assembly (BSA) is a device that reduces the speed of neutrons emitted from a particle accelerator and shapes the beam to match the shape of cancer cells or tumors. An exemplary patent application for this subject matter is TWI712436, “NEUTRON BEAM GENERATING DEVICE.”
(2) Diagnostic and Therapeutic Calculations
When therapy is administered, the location and shape of the tumor must be determined based on tomography images, and the therapy plan must be simulated using computer software. Subsequently, the boron concentration in the patient's blood must be analyzed in accordance with the proposed therapy plan to precisely calculate the radiation dose to be administered. An exemplary patent application for this subject matter is US5,872,107, “TREATMENT OF UROGENITAL CANCER WITH BORON NEUTRON CAPTURE THERAPY.”
(3) Image Recognition Software
Due to advances in image recognition technology, application-specific AI- assisted image recognition software allows specialists to interpret computed tomography (CT) scans of tumors and obtain more accurate locations and shapes of tumors. An exemplary patent application for this subject matter is US11,087,524, “METHOD FOR ESTABLISHING SMOOTH GEOMETRIC MODEL BASED ON DATA OF MEDICAL IMAGE.”
(4) Therapy Plan
Since each patient has different diagnoses and physiological conditions, it is necessary to formulate the most appropriate therapy plan for each patient by computer simulation. For example, a three-dimensional approach may be taken to precisely locate the patient's tumor to the neutron range, and the proper radiation dose to be administered to such patient must be determined. At present, BNCT, due to constraints of the treatment site (nuclear reactor) and the depth of therapy (within 8.5 cm), must rely on computer simulations so as to formulate the therapy plan and refine each therapeutic step. An exemplary patent application for this subject matter is TWI761966, “AN IRRADIATION PARAMETER SELECTION DEVICE AND ITS USING METHOD.”
(5) 10B-containing drugs
A major factor determining the success or failure of BNCT is the 10B-containing drug. It is necessary to confirm that intravenous administration of the 10B-containing drug produces not only a sufficient concentration of 10B in tumor cells but also a higher concentration of 10B in the tumor cells than in normal tissue cells. An exemplary patent application for this subject matter is CN114949215A, “A p-boron phenylalanine nanocrystal, a preparation method thereof, and an application in the preparation of a boron neutron capture drug for treating tumors.”
With regard to the foregoing different technical aspects, an ecosystem has been developed in parallel with international cooperation and competition. At present, the major practitioners or research institutions include those in Taiwan, such as the BNCT Treatment Center of Tsinghua University, Heron Neutron Medical Corp., Taipei Veterans General Hospital, and Taiwan Biotech Co., Ltd; those in China, such as Beijing Kaibaite Polytron Technologies Inc., Neuboron Medical Group (Nanjing) and Xiamen Humanity Hospital; those in Japan, such as CICS, Inc., Kansai BNCT Medical Center, Educational Foundation of Osaka Medical and Pharmaceutical University, Southern Tohoku BNCT Research Center, Sumitomo Heavy Industries, Ltd., and Stella Chemifa Corp.; those in South Korea, such as DAWONSYS; those in the United States, such as Neutron Therapeutics and Tae Life Sciences; and those in Europe, such as RaySearch Laboratories in Sweden and the BNCT Center in Helsinki, Finland. Many of the above institutions have filed applications for patents in the BNCT field.
As of September 2022, the incoPat Global Patent Database lists thousands of patents of BNCT-related technologies from around the world. Analysis of the patent classification numbers and the patent application dates (see Figure [1] below) shows that the main development direction of BNCT technologies lies in the improvement of therapy process of BNCT, instead of the facilities or drugs that used for BNCT.
To address issues related to patents for BNCT therapy methods, particularly the relevant standards on patent eligibility, the authors will discuss the relevant patent drafting practices in the next issue.
