# US 11,439,815 B2 · Protein activity modification > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,439,815 B2 - Document ID: US11439815B2 - Status: Granted - Kind: B2 - Application number: 15/942,637 - Filed: 2018-04-02 - Published: 2018-08-09 - Granted: 2022-09-13 - Earliest claimed: 2003-03-10 - Assignees: Impulse Dynamics NV - Applicants: Impulse Dynamics NV - Inventors: Benny Rousso; Yuval Mika; Hani N. Sabbah; Shlomo Ben-Haim - Web page: https://patentgrep.com/patent/US11439815B2 ## CPC - A61N 1/32: alternating or intermittent currents {(applying electric fields by inductive or capacitive coupling A61N1/40; microwave apparatus A61N5/02)} - A61N 1/205: {for promoting a biological process} - A61N 1/326: {for promoting growth of cells, e.g. bone cells} - C12N 13/00: Treatment of microorganisms or enzymes with electrical or wave energy, e.g. magnetism, sonic waves - A61N 1/3628: {using sub-threshold or non-excitatory signals} - A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B) - C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00) ## Abstract A method of modifying cardiac tissue behavior, comprising applying a therapeutically effective electric field having an effect of modifying protein activation levels of at least one protein, and repeatedly applying the field at time intervals timed to increase the activation levels of the at least one protein beyond an activation level achieved by natural and/or paced excitation of the muscle without the application, to an extent about at least as high as a decay of the activation between applications of the field. ## Claims ### Claim 1 A method of therapy location placement for therapy of a tissue, comprising: selecting a location in the tissue based on a protein activity level at the location; and applying a therapy to the location according to said selecting, wherein said selecting a location based on a protein activity level comprises one or both of: (a) measuring protein activity by applying a test therapy to said or another location in the heart and measuring protein activity or an indication thereof, due to said test therapy; and (b) estimating the effect of a change in protein activity level of tissue at said location using a model of propagation of effect cascading in said heart; and selecting the location based on said measuring or estimating, wherein the method further comprises: deciding on suitability of a location for therapy application by applying a test therapy and deciding on suitability based on an effect on the protein activity levels of said test therapy; selecting a first electrical field parameter that causes an increase in phosphorylation, wherein said applying includes applying an electric field according to said first parameter to thereby cause said increase in phosphorylation and thereby change said protein activity level; choosing a target modification of tissue behavior for at least one of treatment of a disease, short or long term modification of tissue behavior, assessing tissue state and assessing tissue response to stimulation; and wherein said therapy is selected to achieve said modification; measuring an efficacy of achieving said modification with said therapy; further selecting a second electric stimulation parameter for achieving said modification over a longer time frame; and stimulating said tissue with a second electrical field having said second parameter. ### Claim 2 (depends on 1) The method of claim 1, wherein said applying comprises applying according to said selecting and according to an expected change in activity level of existing protein to be caused by said therapy. ### Claim 3 (depends on 1) The method of claim 1, wherein said test therapy is applied outside the body. ### Claim 4 (depends on 1) The method of claim 1, wherein said deciding on suitability of the location of therapy application based on said effect of protein activity levels of said test therapy is when an improvement in organ function is not detected. ### Claim 5 (depends on 1) The method of claim 1, further comprising: placing an electrode at said location after said deciding. ### Claim 6 (depends on 1) The method of claim 1, further comprising: applying another treatment to increase said effect. ### Claim 7 (depends on 1) The method of claim 1, wherein said effect includes phosphorylation. ### Claim 8 (depends on 1) The method of claim 1, wherein said deciding on suitability comprises determining an effect of said test therapy on protein activity level changes which occur within 15 minutes of an application of said test therapy. ### Claim 9 (depends on 1) The method of claim 1, wherein said measuring comprises measuring a phosphorylation level of a protein, which protein is affected in less than 15 minutes by said test therapy. ### Claim 10 (depends on 1) The method of claim 1, further comprising: changing a location of therapy based on said effect of said test therapy. ### Claim 11 (depends on 1) The method of claim 1, wherein said applying is to a location of treatment in an organ the method further comprising: selecting said location of treatment, according to a desired propagation of said treatment in an organ including said tissue. ### Claim 12 (depends on 11) The method of claim 11, wherein said applying is in vivo. ### Claim 13 (depends on 11) The method of claim 11, wherein said propagation is at least one of a mechanical propagation and a biochemical propagation. ### Claim 14 (depends on 11) The method of claim 11, wherein said location comprises a plurality of locations. ### Claim 15 (depends on 1) The method of claim 1, wherein said therapy includes electrical therapy for the heart. ### Claim 16 (depends on 15) The method of claim 15, wherein said applying includes applying a non-excitatory electrical signal to said tissue. ### Claim 17 (depends on 1) The method of claim 1, wherein said further selecting of said second parameter is to affect a gene expression. ### Claim 18 (depends on 1) The method of claim 1, wherein said further selecting of said second parameter is to affect at least one of a mechanical and a functional remodeling of a heart. ### Claim 19 (depends on 1) The method of claim 1, further comprising: measuring an efficacy of achieving said modification with said second electric field; and determining a combination electrical parameter for achieving said modification wherein said combination has at least one of the following advantages: it uses less power than either the first and said second field and it more fully achieves said modification than either said first field or said second field. ### Claim 20 (depends on 1) The method of claim 1, wherein said first and second field applications differ in a least one of power, shape, repetition number, and duration of application. ### Claim 21 (depends on 1) The method of claim 1, wherein said selecting comprises applying a test therapy to said tissue and measuring an effect of said therapy. ### Claim 22 (depends on 1) The method of claim 1, wherein said applying comprises causing a change in activity level of existing protein. ### Claim 23 (depends on 1) The method of claim 1, wherein said selection is applied during electrode implantation, to select an implantation area of electrodes in the heart. ### Claim 24 (depends on 1) The method of claim 1, further wherein said test therapy is applied for less than 100 seconds.