Pulse Biosciences, Inc.

Nanoblate Corp.

Brian G Athos

Mark P Kreis

Richard Lee Nuccitelli

Pamela S Nuccitelli

Jon Berridge

Zachary R Mallon

Darrin R Uecker

Shu Xiao

David J Danitz

Kaying Lui

Joanne Lum

Zachary Mallon

Pamela Nuccitelli

A pulse generation system is disclosed. The pulse generation system includes a controller, an output terminal, and a plurality of pulse generator circuits. The controller is configured to cause a driving signal pulse to be transmitted to any selected one or more of the pulse generator circuits, and to cause the driving signal pulse to not be transmitted to any selected one or more other pulse generator circuits. Each of the pulse generator circuits is configured to generate an output voltage pulse at the output terminal in response to the driving signal pulse being transmitted thereto.

Pulse generator with independent panel triggering

A sub-microsecond pulsed electric field generator is disclosed. The field generator includes a controller, which generates a power supply control signal and generates a pulse generator control signal, and a power supply, which receives the power supply control signal and generates one or more power voltages based on the received power supply control signal. The field generator also includes a pulse generator which receives the power voltages and the pulse generator control signal, and generates one or more pulses based on the power voltages and based on the pulse generator control signal. In some embodiments, the controller receives feedback signals representing a value of a characteristic of or a result of the pulses and generates at least one of the power supply control signal and the pulse generator control signal based on the received feedback signals.

High-voltage circuit pulser

A pulse generator discharge circuit is disclosed. The circuit includes one or more discharge stages, each discharge stage including a plurality of control input terminals. The circuit also includes first and second discharge terminals, and a plurality of serially connected switches electrically connected between the first and second discharge terminals, where a conductive state of each of the switches is controlled by a control signal. The circuit also includes a plurality of inductive elements configured to generate the control signals for the serially connected switches, where each inductive element is configured to generate a control signal for one of the serially connected switches in response to one or more input signals at one or more of the control input terminals, and where each of the serially connected switches is configured to receive a control signal from a respective one of the inductive elements.

High-voltage analog circuit pulser and pulse generator discharge circuit

High-voltage analog circuit pulser

Nanosecond pulsed electric field (nsPEF) treatments of a tumor are adjusted based on a size and type of the tumor to stimulate an immune response against the tumor and other tumors in the subject. Calreticulin expression on tumor cells can be detected to confirm treatment. An immune response biomarker can be measured, and further nsPEF treatments can be performed if needed to stimulate or further stimulate the immune response. Cancers that have metastasized may be treated by directly treating a tumor that is most accessible. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and/or PD-1-blocking antibodies. Electrical characteristics of nsPEF treatments can be based on the size, type, and/or strength of tumors and/or a quantity of tumors in the subject.

Methods and devices for stimulating an immune response using nanosecond pulsed electric fields

Techniques for treating a tumor and vaccinating against cancer are described. The techniques include treating the tumor by positioning electrodes over an interface between the tumor and non-tumor tissue and applying sub-microsecond pulsed electric fields. The positioning is facilitated by an imaginary contour line of a threshold value of the electric field. In an example, the imaginary contour line is overlaid over images that include the tumor such that the electrodes are properly positioned over the tumor. The techniques also include vaccinating against cancer by passing sub-microsecond pulsed electric fields through tumor cells of a subject sufficient to cause the tumor cells to express calreticulin on surface membranes. The tumor cells are extracted and introduced with the expressed calreticulin into the subject or another subject, thereby providing a vaccination.

Nanoelectroablation control and vaccination

A sub-microsecond pulsed electric field generator is disclosed. The field generator includes a controller, which generates a power supply control signal and generates a pulse generator control signal, and a power supply, which receives the power supply control signal and generates one or more power voltages based on the received power supply control signal. The field generator also includes a pulse generator which receives the power voltages and the pulse generator control signal, and generates one or more pulses based on the power voltages and based on the pulse generator control signal. The controller receives feedback signals representing a value of a characteristic of or a result of the pulses and generates at least one of the power supply control signal and the pulse generator control signal based on the received feedback signals.

High-voltage analog circuit pulser with feedback control

A subject is inoculated from a disease by exposing a biopsy of a tumor or other abnormal growth to a nanosecond pulsed electric field (nsPEF). A sufficient treatment can be confirmed by detecting calreticulin on the tumor cell membranes, which indicates apoptosis occurring in the tumor cells. Treated tumor cells from the biopsy are then reintroduced into the subject. The calreticulin-exhibiting tumor cells activate the subject's immune system against the tumor, and any other like tumors in the body, and effectively vaccinates the subject against the disease. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and/or PD-1-blocking antibodies. The immune response may be measured at a later time. Specific electrical characteristics of the nsPEF treatments can be based on the type and/or strength of the tumor.

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San Francisco, CA, United States of America

Brian G Athos