# US 11,079,288 B2 · Analysis of calorimetry measurements > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,079,288 B2 - Document ID: US11079288B2 - Status: Granted - Kind: B2 - Application number: 16/484,685 - Filed: 2018-01-31 - Published: 2020-05-21 - Granted: 2021-08-03 - Earliest claimed: 2017-02-14 - Assignees: Malvern Panalytical Limited - Applicants: Malvern Panalytical Inc. - Inventors: Benjamin Edward Pattison; Kenneth Haber; Mark Arsenault - Web page: https://patentgrep.com/patent/US11079288B2 ## CPC - G01K 17/006: {Microcalorimeters, e.g. using silicon microstructures} - G01N 25/4866: {by using a differential method} - G01K: MEASURING TEMPERATURE; MEASURING QUANTITY OF HEAT; THERMALLY-SENSITIVE ELEMENTS NOT OTHERWISE PROVIDED FOR (radiation pyrometry G01J5/00) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) ## Abstract A method determining a degree of similarity between a first sample and a second sample, comprising using a processor to compare a first thermogram and a second thermogram, each obtained by performing scanning calorimetry on a first and second sample respectively, by: determining a smoothed first thermogram and a smoothed second thermogram by respectively performing a smoothing operation on the first thermogram and the second thermogram; determining a processed first thermogram and a processed second thermogram by respectively finding a derivative of the smoothed first thermogram and the smoothed second thermogram; determining the degree of similarity from a correlation operation comparing the processed first thermogram with the processed second thermogram. ## Claims ### Claim 1 A method of determining a degree of similarity between a first sample and a second sample, comprising using a processor to compare a first thermogram and a second thermogram, each obtained by performing scanning calorimetry on the first and second sample respectively, by: determining a smoothed first thermogram and a smoothed second thermogram by respectively performing a smoothing operation on the first thermogram and the second thermogram; determining a processed first thermogram and a processed second thermogram by respectively finding a derivative of the smoothed first thermogram and the smoothed second thermogram; determining the degree of similarity from a correlation operation comparing the processed first thermogram with the processed second thermogram. ### Claim 2 (depends on 1) The method of claim 1, wherein finding the derivative comprises finding a second derivative. ### Claim 3 (depends on 1) The method of claim 1, wherein performing the smoothing operation comprises performing Savitzky-Golay smoothing. ### Claim 4 (depends on 3) The method of claim 3, wherein the Savitzky-Golay smoothing utilises cubic polynomial fits. ### Claim 5 (depends on 1) The method of claim 1, wherein performing the smoothing operation comprises finding a moving average. ### Claim 6 (depends on 1) The method of claim 1, wherein performing the correlation operation comprises determining a Pearson correlation between the processed second thermogram and the processed first thermogram. ### Claim 7 (depends on 1) The method of claim 1, wherein performing the correlation operation comprises determining a Pearson distance between the processed first thermogram and the processed second thermogram. ### Claim 8 (depends on 1) The method of claim 1, further comprising the step of determining the first thermogram and/or second thermogram by calorimetry. ### Claim 9 (depends on 8) The method of claim 8, wherein the step of determining the first thermogram and/or second thermogram comprises performing a differential scanning microcalorimetry measurement. ### Claim 10 (depends on 1) The method of claim 1, wherein the first and second sample comprise a candidate biopharmaceutical. ### Claim 11 (depends on 1) The method of claim 1, wherein the degree of similarity is a degree of biosimilarity. ### Claim 12 (depends on 1) The method of claim 1, wherein determining a degree of similarity from a correlation operation comprises weighting a result of the correlation operation by a degree of similarity between values of a physical parameter determined from the first thermogram and second thermogram. ### Claim 13 (depends on 12) The method of claim 12, wherein the physical parameter is selected from: a state transition temperature, a state transition enthalpy, and a state transition cooperativity. ### Claim 14 (depends on 13) The method of claim 13, wherein the state transition is: a melting point, a denaturation point or a folding/unfolding temperature. ### Claim 15 (depends on 1) The method of claim 1, wherein determining a degree of similarity from a correlation operation comprises exponentiating a result of the correlation operation. ### Claim 16 (depends on 1) A machine readable non-transient storage medium, comprising instructions for configuring a computer to perform the method of claim 1. ### Claim 17 A differential scanning calorimeter operable to obtain a thermogram from a sample, comprising: a sample cell, a reference cell, a thermal shield disposed around the sample cell and the reference cell, a cell heater arranged to heat the sample cell and the reference cell, a thermal sensor arranged to measure a difference in temperature between the sample cell and the reference cell, and a processing system configured to control the cell heater and receive temperature measurements from the sample cell and reference cell, and to determine a first thermogram comprising estimates of heat capacity at each of a range of temperatures for a test substance in the sample cell, the estimates being responsive to a difference in the amount of heat required to maintain the sample cell and reference cell at the same temperature while the temperature of both the sample cell and reference cell is varied, wherein the processing system comprises a memory for storing a second thermogram, and the processing system is configured to compare the first thermogram with the second thermogram, by: determining a smoothed first thermogram and a smoothed second thermogram by respectively performing a smoothing operation on the first thermogram and the second thermogram; determining a processed first thermogram and a processed second thermogram by respectively finding a derivative of the smoothed first thermogram and the smoothed second thermogram; determining the degree of similarity from a correlation operation comparing the processed first thermogram with the processed second thermogram.