Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Detailed Action
Summary
This is the Final Office Action based on application 18/669414 RCE response filed 10/17/2025.
Claims 1-19, 22, 24-28 & 30-34 have been elected, and fully considered.
Claims 20-21, 23 are withdrawn.
Claim 29 is cancelled.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition ofmatter, or any new and useful improvement thereof, may obtain a patent therefor, subject to theconditions and requirements of this title.
The claimed invention of Claims 1-19, 22, & 24-28 & 30-34 are directed to non-statutory subject matter.
The invention of instant claims is drawn towards a method for determining a characteristic property of molecular interaction.
Through 101, inquiry:
Inquiry: Is the claim directed to a statutory category of invention?
Yes, independent Claims 1, 4, & 22 are drawn towards a statutory category (a method).
Step 2A, Prong 1: Do the claims involve a Judicial Exception?
Yes, independent Claims 1, 4, & 22 and those that depend therefrom involve the judicial exception of an abstract idea.
Claims 1, 4, & 22 require, “determining a characteristic property,” and “determining said characteristic property, in the preamble and claim body. “Determining,” as claimed, is mental processes, which is an abstract idea judicial exception.
Step 2A, Prong: Has the abstract idea been integrated into a particular practical application? Step 2B: Does the claim recite any elements which are significantly more than the abstract idea?
For Claim 1, the answer is no.
Claim 1 includes the additional steps of:
Providing a liquid sample comprising a particle and a binding partner in a solvent (that are capable of being in equilibrium or non-equilibrium). This can read on many natural things. For example, providing a blood sample that contains protein (particle) and antibodies (binding partner); or a blood sample that contains red blood cells (particle) and hemoglobin (binding partner). Therefore, as broadly claimed--- this can read on providing a liquid sample (blood)- which is a product of nature- which is another judicial exception, and the solvent can read on water, so providing a diluted sample. Therefore, the claimed providing of a sample (a diluted sample), is just used to gather data to perform the abstract idea of “determining”. Data gathering has been shown to be insignificant extra-solution activity, see MPEP 2106.05 (g) and therefore does nothing to practically apply. Further, providing a sample as is done is well understood, routine and conventional (WURC) in the art and therefore does it add significantly more to it. See MPEP 2106.05(d).
Bringing the particle into a state of equilibrium and subjecting the sample to a condition jump. This is then further limited to that the condition jump is a temperature jump that is brought on by a “heating or cooling arrangement,” and that the liquid is maintained at the second temperature during the detecting. A “heating or cooling arrangement,” can be something simple like a fire or snow/ice. It could also be some kind of unspecified device that is not claimed. Therefore, through BRI- the claimed “arrangement,” and the resulting condition jump can be a natural occurrence to a product of nature (in the example the examiner is using the sample is blood). Therefore, this does nothing to practically apply the judicial exception. Also, heating and cooling arrangements are well understood routine and conventional in the art, therefore does not add significantly more to it.
Detecting optical signals or electrochemical signals of a marker of the particle- wherein the detecting is performed by an optical reader arrangement or an electrochemical reader arrangement, and wherein this includes performing two or more readings as a function of time from different fractions of the sample as the sample is flowing in a reading section of a microfluidic unit. The instant “detecting,” is done to use the judicial exception—“determining a characteristic property,” and gather data to perform it. Data gathering has been shown to be insignificant extra solution activity so does not practically apply. See MPEP 2106.05 (g).
Nothing is done in the claim after the very broadly claimed measurement/detection and therefore there is not practical application. Further, both optical and electrochemical readers are routine and conventional detection devices in the art—therefore do not add enough to practically apply or add significantly more to the judicial exception, especially at the level of generality claimed. This holds true when a microfluidic unit is used to detect a flowing sample as this is also well understood routine and conventional in the art and therefore does not make the claims significantly more. See MPEP 2106.05 (d).
Determining the characteristic property of the molecular interaction based on the optical or electrochemical signal of the marker as a function of time. This determining as claimed is a mental process at simplest and math at most as claimed. That the second temperature is homogenous in an entirety of the sample, does not change this. Therefore, is an abstract idea, and therefore does not practically apply the judicial exception or add significantly more to it.
Further—it is noted that in all of the independent claims after the “detecting”, is done— nothing is done with the detection results other than the judicial exception itself, “determining,” to practically apply it. Also, as claimed providing a liquid sample and bringing the particle in a sample into non-equilibrium by subjecting to a condition jump appear to be extra pre-solution activity (data gathering – see MPEP 2106.05(g)), for the claimed abstract idea judicial exception. Therefore, there is no particular practical integration at step 2A, 2, and there is nothing added which is significantly more at step 2B.
Claim 4- it carries mostly the same analysis as for Claim 1. Claim 4 adds limitations including:
That the optical signals are detected during a relaxation time.
This does not change the fact that optical signals and signal detection are used as a data pull, so this is still considered insignificant extra-solution activity so does not practically apply at step 2A, 2 and optical signals and detection is routine and conventional in the art, so does not add significantly more to the judicial exception.
That the liquid sample is non-diluted;
If blood is the liquid sample in question here as per the example the examiner gave above, blood is routinely used in the art without dilution. This is not doing anything to practically apply at step 2 A, 2, and also does not add significantly more to the judicial exception.
That the particle has a structure which differs in structure at the second condition after the condition jump from what it was prior to the condition jump (and that this structure difference is a protein folding change).
With respect to this, all proteins have structures which can denature when exposed to high heat or just the regular heat of a hot dat. Therefore, this is a natural occurrence and therefore does nothing practically apply at step 2A, 2 nor does it add significantly more to the judicial exception at step 2B. That the second temperature is homogenous in an entirety of the sample, does not change this.
For Claim 22— it carries mostly the same analysis as is shown above for Claim 1, but it contains an additional limitation in that it is further required that the detecting of optical signals is done, “as a function of time comprising at least two optical detections of intensity of more than one wavelength from the point of time where the particles are subjected to the condition jump wherein the more than one wavelength comprises a change of wavelength.” Optical detections of wavelengths are routine and conventional detection devices in the art—therefore do not add enough to practically apply or add significantly more to the judicial exception, especially at the level of generality claimed. This remains the case even with the generally added, “as the sample is flowing at a velocity in a reading section of a microfluidic unit and where the method comprises reducing the velocity.”
Therefore, the independent claims 1, 4, & 22 do not recite significantly more than the abstract idea.
Dependent claims
For the dependent claims we would look to see if they add limitations that change the above analysis (e.g. does the new limitation integrate into a practical application or amount to significantly more?). Here, none of the dependent claims 2-19 or 24-34 integrate the abstract idea or amount to significantly more.
Claim 2 recites more specification on the claimed detecting, specifying that it is performed in a few different fractions. This is akin to claimed repeating of a process. Therefore, this remains routine and conventional in the art, especially at the level of generality it is claimed at.
Claim 3 recites more specification on what is meant by the particle being capable of being in equilibrium- and that the sample contains both particle and binding partner. However- at the level of generality claimed—both these pieces seem to be present in the initial sample (for instance, in water) and therefore this does nothing to integrate or add significantly more.
Claims 5 & 33 specify that the conformation (spatial arrangement of constituent atoms) of the particle (protein) changes after the condition jump. Again- this is something that routinely and naturally happens to proteins when temperature changes occur, and it is a material property that the “signal,” of the marker of the particle would change as well. Therefore, this is something that naturally occurs. Therefore, does not practically apply or add significantly more to the judicial exception.
Claim 6 specifies that the condition jump is performed in a microfluidic unit and that the microfluidic unit is partly in a temperature-controlled compartment. However- this is very general and at the level of generality claimed—it is routine and conventional to provide and us a somewhat temperature controlled microfluidic unit. Therefore- this does not practically apply or add significantly more to the abstract idea.
Claim 7 specifies that the microfluidic unit and that the microfluidic unit comprises a capillary channel with an introduction section that has a cross section of 1 mm or less. However as claimed, this is extra solution activity— an uses a routine and conventional device (microfluidic device). Size of an introduction does not change this as under 1mm is routine for microfluidic units, and this is also not considered analysis with a particular device. Therefore- this does not practically apply or add significantly more to the abstract idea.
Claim 8 specifies that the second temperature is maintained during the relaxation time and during the detecting of the optical or electrochemical signals (which is only mentioned in Claim 1 which Claim 8 depends upon with respect to the “reading out,” clause. Therefore, that the reading occurs at the second temperature during the relaxation time does not change the fact that the reading is an abstract idea, nor does it practically apply or add significantly more to the judicial exception.
Claim 9 specifies that the temperature control can be done by blowing air--- which can occur naturally in nature—any flow of air can be considered blowing air. Therefore, especially at the level of generality claimed, this routine and conventional in the art and does not practically apply or add significantly more to the judicial exception.
Claim 10 specifies that the temperature jump is at least 2 degrees. Again- temperature jumps are something that naturally occurs—for example as the day turns from morning to afternoon. Therefore, this is routine and conventional and not enough to turn the judicial exception into a practical application or significantly more.
Claim 11& 30 specify that the second temperature is from about 5 degrees Celsius (41 Fahrenheit) to about 50 degrees Celsius (122 degrees Fahrenheit) and that the temperature jump is 5 degrees. Again- temperature jumps are something that naturally occurs—for example as the day turns from morning to afternoon and the temperature at the later half of the day often falls above 50 degrees. Therefore, this is routine and conventional and not enough to turn the judicial exception into a practical application or significantly more.
Claim 12 specifies that the microfluidic unit comprises a channel with an introduction section and reading section and that detecting occurs while sample is flowing through microfluidic device. Microfluidic devices having inlets and analysis section are routine and common in the art and especially at the level of generality claimed--- these limitations do not integrate the judicial exception into a practical application or add significantly more.
Claim 13 specifies that detecting of consecutive samples happens at different times as the sample is flowing at an unspecified velocity in the channel. Again- the claimed detecting is routine and conventional in the art, especially at the level of generality claimed so this does not practically apply or add significantly more to the judicial exception.
Claim 14, specifies that a parameter is determined from the claimed analysis and gives options for what the parameter is. However- the claimed determining is a mental process, and the parameters as claimed at the level of generality claimed do not add significantly more or practically apply. It is not claimed how the determining is done.
Claim 15 specifies that the molecular interaction is liquid-liquid phase separation. This is something that naturally occurs if two immiscible liquids are used for example, water and oil. Therefore, determining liquid liquid phase separation by the method of Claim 1 & 6 does not practically apply the judicial exception or make it significantly more—at least at the level of generality claimed specifically in Claim 1.
Claim 16 specifies that prior to the condition jump the liquid is in one phase. Again- due to the generality at which Claim 1 is claimed using “condition jump,” and “molecular interaction,” among other things, specifying that one phase is used for a liquid at that level of generality is not enough to be considered to practically apply the judicial exception. For example- a one phase liquid could be a water/oil mix that is shook up, then separates during the phase separation.
Claim 17, specifies that the liquid phases differ from each other. Liquids which differ from each other is a given in phase separation, therefore this is routine and not enough to apply or make significantly more than the judicial exception.
Claim 18, specifies that the temperature jump is from a higher to lower temperature. Again- temperature jumps occur in nature, and therefore this is routine and conventional and not enough to apply or more the judicial exception significantly more. Also, there is no practical application here.
Claim 19 specifies that the microfluidic unit comprises a channel and that reading out section and that reading out occurs while sample is flowing through the channel and that the detecting is performed multiple times from different fractions of the sample as a sample is flowing through the microfluidic unit and passing the reading location and wherein at an unspecified time the velocity is slowed down. Microfluidic devices having channels are routine and common in the art and especially at the level of generality claimed, including that the sample is fed at a “pressure,” at a “velocity” and that velocity is adjustable in that it slows down as flowing through the channel--- these limitations do not integrate the judicial exception into a practical application or add significantly more.
Claim 24 specifies that the detecting occurs during the relaxation time. This does not change the fact that optical signals and signal detection is routine and conventional in the art, and as claimed are being used as a data pull. Therefore this does not add significantly more or practically apply the judicial exception.
Claim 25 species what the temperature is during the detecting. Again- the detecting as claimed is routine and conventional and temperatures also rise from a first to second temperature then maintain at a second temperature throughout the course of a day. Therefore, this is a natural occurrence so does not practically apply or make the judicial exception significantly more.
Claims 26-27 species that the detecting includes reading of a change in wavelength intensity. Detecting wavelength intensity is routine and conventional in the art and is still being used as a data pull, therefore, does not change this nor does it practically apply or make the judicial exception significantly more.
Claim 28 specifies that the temperature jump happens in a capillary tube. Capillary tubes are routinely and conventionally used in the art. Therefore, at the level of generality claimed does not practically apply or make the judicial exception significantly more.
Claim 31 specifies that the jump time for the condition jump is 1 minute or less. Here applicant seems to be claiming that the particles are exposed to heat, or that the particle conformation changes happen in 1 minute. The particle conformation is a material property of a natural compound therefore is a product of nature. Exposing to heat is something that also naturally occurs throughout the course of a day. Therefore this does not add significantly more or practically apply the judicial exception.
minute. This is specifying that the detection is a “reading,” which is an abstract idea/mental process and therefore does not do anything to practically apply or add significantly more to the judicial exception.
With respect to Claim 34, it specifies that the second temperature is a temperature that is the same throughout the entire sample. This does nothing to practically apply. Also many/most object have the same temperature throughout through the laws of thermodynamics. Therefore, this is WURC and does not add significantly more.
See MPEP 2106.04 & 2106.05. In re Alappat; Also, process claims that are directed to abstract ideas, such as the claims in Bilski v. Kappos & MPEP § 2106.01. Also see Parker v. Flook, and also Alice.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-6, 8, 10-14, 22, 24-28, 30 & 33 are rejected under 35 U.S.C. 103 as being obvious by PEARSON in A novel pressure-jump apparatus for the microvolume analysis of protein-ligand and protein-protein interactions: its application to nucleotide binding to skeletal-muscle and smooth- muscle mysosin subfragment-1 in view of HADDAD in US 20170168077 and in further view of WEIGL in US 20020090644.
With respect to Claim 1, PEARSON teaches of a method for determining a characteristic property of a molecular interaction (protein-ligand interactions between rabbit skeletal muscle-derived myosin fragment skS1 and ADP), the method comprising:
providing a liquid sample comprising a particle capable of being in a state of equilibrium and in a state of non-equilibrium (ADP), the particle comprises a marker in at least one of its state of equilibrium and state of non-equilibrium (has fluorescent marking),
bringing the particle in a state of non-equilibrium by subjecting the sample to a condition jump comprising a jump in pressure from a first pressure (0.6MPa) to a second pressure (10MPa), reading out said marker as a function of time during at least a portion of a relaxation time for said particle (see figure 4). It is noted that in both liquids and in gases, when the pressure changes/goes up the temperature changes/goes up. For gases this can be seen through the ideal gas law P(pressure)V (volume)= n (number of mole) R (ideal gas constant) T(temperature). Therefore, if pressure goes up so does temperature, and though the effect is not as pronounced in liquids as in gas—the same thing happens for liquids.
determining said characteristic property of said molecular interaction, wherein said reading out comprises reading out as a function of time comprising performing two or more readings from different fractions of said sample (see figure 4), in a microfluidic unit (the size of the apparatus is within the micro- ranges and is therefore a microfluidic device; see figure 1) (PEARSON, abstract; page 646, right-hand column, paragraph 3 and figure 4).
PEARSON further teaches an apparatus associated with this method for determining a characteristic property of a molecular interaction, and comprising
a sample compartment for containing at least one liquid mother sample;
a withdrawing arrangement arranged for withdrawing a sample from a at least one mother sample stored in said sample compartment;
a condition jump arrangement arranged for performing a jump in pressure from a first pressure to a second pressure, and
at least one reader arrangement for reading at least one marker as a function of time, wherein the apparatus can perform reading out as a function of time by performing two or more readings from different fractions of said sample, with the sample contained in a microfluidic unit (abstract, pages 644-645 and figure 1, Figure 3, 4, 6).
PEARSON teaches of detecting changes in conformation as a result in the changes in condition jump/change (which in this case is a pressure jump/change—which leads to temperature change/jump due to the relationship between pressure and temperature in any closed system) and this is due to binding and conformation changes. The changes detected are fluorescent/optical signals/changes by an optical/fluorescent signal reader. (Page 650, column 2, paragraph 3, line 7 & on & Page 644, column 1, paragraph). This results in a change in fluorescence signal due to fluorescent marker (abstract). Figure 1 shows the pressure jump apparatus and the microfluidic inlet.
If the condition jump being a temperature jump and the temperature arrangement (heating or cooling arrangement) is unclear to one of ordinary skill in the art from PEARSON, HADDAD is used to remedy this. PEARSON also does not teach of slowing the velocity of fluid flow.
HADDAD teaches of a method of analysis of a sample (abstract). HADDAD further teaches of the device used being microfluidic (paragraph 0003), and that the assays the device is used for might depend on temperature (paragraph 0034), and that the device allows for detection in an incubation channel (paragraph 0036). HADDAD further teaches that in some instances the channel states at one temperature and then is reduced in temperature in the detection step and in some instances the temperature is increased (paragraph 0055-0056). Both of these involve a first temperature and second temperature read on subjecting the sample to a “condition jump,” as claimed.
HADDAD further teaches of a heater (heating arrangement) being used to heat the fluid in the microfluidic device (paragraph 0214-0217). HADDAD teaches that the whole sample is heated to specific degrees (for example 60, 25, 25), of temperatures--- so this reads on the sample having a homogenous temperature.
HADDAD also teaches of slowing the flow rate/velocity of the fluid flowing through the device (paragraph 0054).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use a temperature jump as the condition jump and a heating arrangement as is done in HADDAD in the method of PEARSON due to the advantage changing and controlling temperature offers for controlling assay sensitivity (paragraph 0034) and it would have been obvious to slow velocity/fluid flow since the flow rates and adjustments are determined based on the assay and sample components and due to the advantage the method of HADDAD allows for slowing or stoppage of fluid flow without negatively influencing subsequent actions (HADDAD, paragraph 0054).
PEARSON and HADDAD teaches of the claimed invention as shown above. They do not teach of making two or more readings from different fractions of the sample.
WEIGL is used to remedy this and further teaches of methods and apparatuses are provided for determining presence and concentration of analytes by exploiting molecular binding reactions and differential diffusion rates(abstract). WEIGL further teaches of performing the method in batch mode using multiple sample aliquots (fractions)(paragraph 0053), and of using a computer or processor to analyze/determine/read the presence of the analyte particles (paragraph 0052). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use sample aliquots or fractions as is done in WEIGL in the methods of PEARSON and HADDAD due to the advantage this offers in comparing a profile of streams or samples (WEIGL, paragraph 0052).
With respect to Claim 2, PEARSON and HADDAD teaches of the claimed invention as shown above. They do not teach of making two or more readings from different fractions of the sample.
WEIGL is used to remedy this and further teaches of methods and apparatuses are provided for determining presence and concentration of analytes by exploiting molecular binding reactions and differential diffusion rates(abstract). WEIGL further teaches of performing the method in batch mode using multiple sample aliquots (fractions)(paragraph 0053), and of using a computer or processor to analyze/determine/read the presence of the analyte particles (paragraph 0052). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use sample aliquots or fractions as is done in WEIGL in the methods of PEARSON and HADDAD due to the advantage this offers in comparing a profile of streams or samples (WEIGL, paragraph 0052).
With respect to Claim 4, PEARSON teaches of the invention as shown above.
PEARSON does not teach that the sample is non-diluted. HADDAD is used to remedy this.
HADDAD is used to remedy this and teaches that the two assay somponet sin the channel can be the sample component and reagent (no dilutent)(paragraph 0035).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use the non-diluted sample and have them in the channel/ flow through method as is done in HADDAD in the method of PEARSON due to the advantage it allows for sample incubation or mixing of components (HADDAD, paragraph 0036).
PEARSON and HADDAD teaches of the claimed invention as shown above. They do not teach of making two or more readings from different fractions of the sample.
WEIGL is used to remedy this and further teaches of methods and apparatuses are provided for determining presence and concentration of analytes by exploiting molecular binding reactions and differential diffusion rates(abstract). WEIGL further teaches of performing the method in batch mode using multiple sample aliquots (fractions)(paragraph 0053), and of using a computer or processor to analyze/determine/read the presence of the analyte particles (paragraph 0052). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use sample aliquots or fractions as is done in WEIGL in the methods of PEARSON and HADDAD due to the advantage this offers in comparing a profile of streams or samples (WEIGL, paragraph 0052).
With respect to Claims 5 & 33, PEARSON teaches of detecting changes in conformation as a result in the changes in condition jump/change (which in this case is a pressure jump/change—which leads to temperature change/jump) (Page 650, column 2, paragraph 3, line 7 & on & Page 644, column 1, paragraph 7). This results in a change in fluorescence signal (abstract). Figure 1 shows the pressure jump apparatus and the microfluidic inlet.
With respect to Claim 6, PEARSON teaches of detecting changes in conformation as a result in the changes in condition jump/change (which in this case is a pressure jump/change—which leads to temperature change/jump) (Page 650, column 2, paragraph 3, line 7 & on & Page 644, column 1, paragraph). This results in a change in fluorescence signal (abstract). Figure 1 shows the pressure jump apparatus and the microfluidic inlet.
With respect to Claim 8, PEARSON teaches of detecting changes in conformation as a result in the changes in condition jump/change (which in this case is a pressure jump/change—which leads to temperature change/jump) (Page 650, column 2, paragraph 3, line 7 & on & Page 644, column 1, paragraph). This results in a change in fluorescence signal (abstract). Figure 1 shows the pressure jump apparatus and the microfluidic inlet.
With respect to Claim 10 & 30, HADDAD teaches that the temperature jumps can be more than 2 degrees Celsius (paragraphs 0055-0056).
With respect to Claim 11, HADDAD teaches that the temperature jumps can be more than 2 degrees Celsius and in the claimed range of 5 to 50 degrees Celsius (paragraphs 0055-0056).
With respect to Claims 12-13, PEARSON teaches of the above and further teaches of the device having an inlet/introduction section (see Figure 1). If it is unclear that PEARSON and HADDAD teach of the claimed detecting/reading as claimed WEIGL is used to remedy this.
WEIGL teaches of the device having inlets (paragraph 0012-0014). WEIGL further teaches of performing the method in batch mode using multiple sample aliquots (fractions) as they flow through the device (paragraph 0053), and of using a computer or processor to analyze/determine/read the presence of the analyte particles (paragraph 0052) and making the readings as a function of time (paragraph 0039, 0041, 0078, 0087). WEIGL also teach of measuring/detecting (reading) at the junction using detector arrays (paragraph 0092). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use sample aliquots or fractions and monitor over time as is done in WEIGL in the method of PEARSON and HADDAD due to the advantage this offers in comparing a profile of streams or samples (WEIGL, paragraph 0052).
With respect to Claim 14, PEARSON teaches of determining a kinetic parameter (abstract).
With respect to Claim 22, PEARSON and HADDAD teaches of the invention as shown for Claim 1 as shown above.
PEARSON and HADDAD does not teach of detecting wavelengths intensity specifically, WEIGL is used to remedy this.
WEIGL teaches of detecting fluorescence intensity for the binding of the particles (paragraph 0040, 0023, 0045, 0051) and specifically of detecting wavelengths including a range/change or different wavelengths/intensities depending on binding (paragraph 0094, 0045).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect wavelengths for fluorescence as is done in WEIGL in the method of PEARSON and HADDAD due to the advantages optical detection offer for visible detection of reaction (WEIGL, paragraph 0045, 0005).
With respect to Claim 24, PEARSON teaches of detecting and measuring as a function of time and of there being relaxation time when there is not change (See Figure 2 as associated description).
With respect to Claim 25, PEARSON teaches of the claim as shown above. If the condition jump being a temperature jump is unclear to one of ordinary skill in the art from PEARSON, HADDAD is used to remedy this.
HADDAD teaches of a method of analysis of a sample (abstract). HADDAD further teaches of the device used being microfluidic (paragraph 0003), and that the assays the device is used for might depend on temperature (paragraph 0034), and that the device allows for detection in an incubation channel (paragraph 0036). HADDAD further teaches that in some instances the channel states at one temperature and then is reduced in temperature in the detection step and in some instances the temperature is increased (paragraph 0055-0056). Both of these involve a first temperature and second temperature read on subjecting the sample to a “condition jump,” as claimed.
HADDAD further teaches of a heater (heating arrangement) being used to heat the fluid in the microfluidic device (paragraph 0214-0217). HADDAD teaches that the whole sample is heated to specific degrees (for example 60, 25, 25), of temperatures--- so this reads on the sample having a homogenous temperature.
HADDAD also teaches of slowing the flow rate/velocity of the fluid flowing through the device (paragraph 0054).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use a temperature jump as the condition jump and a heating arrangement as is done in HADDAD in the method of PEARSON due to the advantage changing and controlling temperature offers for controlling assay sensitivity (paragraph 0034) and it would have been obvious to slow velocity/fluid flow since the flow rates and adjustments are determined based on the assay and sample components and due to the advantage the method of HADDAD allows for slowing or stoppage of fluid flow without negatively influencing subsequent actions (HADDAD, paragraph 0054).
With respect to Claims 26-27, PEARSON does not teach of detecting change in intensity of wavelengths. HADDAD teaches of detecting wavelengths (paragraph 0189), but does not teach of detecting wavelength intensity.
WEIGL is used to remedy this and further teaches of performing the method in batch mode using multiple sample aliquots (fractions) as they flow through the device (paragraph 0053), and of using a computer or processor to analyze/determine/read the presence of the analyte particles (paragraph 0052) and making the readings as a function of time (paragraph 0039, 0041, 0078, 0087). WEIGL also teach of measuring/detecting (reading) at the junction using detector arrays (paragraph 0092). WEIGL teaches of detecting fluorescence intensity for the binding of the particles (paragraph 0040, 0023, 0045, 0051) and specifically of detecting wavelengths including a range/change/shift or different wavelengths/intensities depending on binding (paragraph 0094, 0045).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to detect wavelengths for fluorescence as is done in WEIGL in the method of PEARSON and HADDAD due to the advantages optical detection offer for visible detection of reaction (WEIGL, paragraph 0045, 0005).
With respect to Claim 28, PEARSON teaches of the above, but does not teach of using a capillary tube. HADDAD is used to remedy this and teaches of using tubes (paragraph 0167) and the capillary forces work to draw blood into channel so it is a capillary tube (paragraph 0040). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use capillary tubes for the samples as is done in HADDAD in the method of PEARSON due to the advantage they offer for drawing blood into channels (HADDAD, paragraph 0040).
Claims 7, 9, 15-19, 31, 32, & 34 are rejected under 35 U.S.C. 103 as being unpatentable over PEARSON in A novel pressure-jump apparatus for the microvolume analysis of protein-ligand and protein-protein interactions: its application to nucleotide binding to skeletal-muscle and smooth- muscle mysosin subfragment-1 in view of HADDAD in US 20170168077 in further view of WEIGL in US 20020090644 and further in view of YANG in US 20220003661.
With respect to Claim 7, PEARSON and HADDAD and WEIGL teaches of the invention as shown above. They do not teach of the dimensions of the capillary.
YANG is used to remedy this and teaches of loading the sample into a capillary with dimensions of 1 mm by 1 mm (paragraph 0182). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use the capillaries the size used in YANG in the method of PEARSON and HADDAD and WEIGL due to the advantage this has as being a readily available (VitroCom) capillary (paragraph 0182).
With respect to Claim 9, PEARSON and HADDAD and WEIGL teaches of the claimed invention as shown above, but however does not teach of controlling the temperature by blowing air or by fill level.
YANG is used to remedy this and teaches that as liquid droplets grow/increase temperatures decrease (therefore teaches of the fill level in the device controlling temperature) (paragraph 0156). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to control the temperature by fill level as is done in YANG in the method of PEARSON and HADDAD and WEIGL due to the advantage this has for controlling reaction kinetics (YANG, paragraph 0156).
With respect to Claim 15, PEARSON and HADDAD and WEIGL teaches of the claimed invention as shown above for Claim 1 and 6. PEARSON and HADDAD and WEIGL does not teach of the molecular interaction being liquid liquid phase separation.
YANG is used to remedy this and further teaches of methods for characterizing kinetics and thermodynamics of solutions containing macromolecules over a range of concentrations, temperatures, pH, and added excipients in order to improve their long term stability(abstract). YANG more specifically teaches of performing temperature or condition jump experiments to study the kinetics of phase separation (paragraph 0037), and specifically of determining liquid-liquid phase separation (paragraph 0157). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to determine liquid liquid phase separation as is done in YANG in the methods of PEARSON and HADDAD and WEIGL due to the advantage it offers as a metric for stability in biologics formation studies (YANG, paragraph 0157).
With respect to Claim 16, See the above rejection for Claim 15. YANG further teaches of the liquid liquid phase separation being a homogenous liquid demixing into two phases (paragraph 0157) and of doing temperature jump experiments (paragraph 0037). See reason for combination for Claim 15.
With respect to Claim 17, see above rejection for Claims 15 & 16. YANG further teaches of determining concentrations differences between the phases (paragraph 0196). See reason for combination for Claim 15.
With respect to Claim 18, PEARSON teaches the invention as shown above. It does not teach of making a temperature jump from high to low temperature. HADDAD is used to remedy this and teach of the temperature jump being from high in middle to low at the end (paragraph 0037). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to perform a temperature jump this way as is done in HADDAD in the method of HADDAD due to the advantage it offers with respect to some types of analysis (HADDAD, paragraph 0037).
With respect to Claim 19, PEARSON teaches of feeding the sample to the channel at pressure (this ensures a selected velocity) and change in pressure also means that change in velocity is also possible (due to the laws of physics and fluid dynamics when pressure decreases, velocity decreases) (abstract, Figure 1).
With respect to Claim 31, PEARSON and HADDAD and WEIGL teach of the invention as shown above, but they do not teach of the condition jump taking 1 minute or less.
YANG is used to remedy this and further teaches of establishing a temperature gradient across a holder holding a sample- wherein the temperature stabilizes in 1 minute (paragraph 0006) and that the phase separation temperature (condition jump) happens after 1 minute (paragraph 0048). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to subject the sample to a temperature to perform a condition jump in 1 minute or less as is done in YANG in the method of PEARSON and HADDAD and WEIGL due to the advantage this has for giving information for reaction kinetic study (YANG, paragraph 0048).
With respect to Claim 32, PEARSON and HADDAD and WEIGL does not call out making 5 readings per minute.
YANG is used to remedy this and teaches of making continuous measurements ( so more than 5 readings per minute (paragraph 0048, 0170 Figure 32, 0082). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to make continuous measurements as is done in YANG in the method of PEARSON and HADDAD and WEIGL due to the advantage it has for studying temperature dependent reaction kinetics (YANG, paragraph 0082).
With respect to Claim 34, PEARSON and HADDAD and WEIGL do not teach of using homogenous or steady state temperature. YANG is used to remedy this and teaches of using steady state temperature (paragraph 0023). It would have been obvious to one of ordinary skill in the art before the effective filing date of the instant invention to use steady state temperature as is done in YANG in the method of PEARSON and HADDAD and WEIGL due to the advantage this for determining reaction kinetics (paragraph 0023, 0105, 0114).
Response to Arguments
Applicant's arguments filed 10/17/2025 have been fully considered but they are not persuasive.
It is noted that the claims submitted 10/17/2025 are different from what was proposed and attached to the interview summary- in the file wrapper dated 10/21/2025. As the proposed amendments for the interview were only for discussion purposes, the examiner is noting that they are significantly different from what was filed, which contain less substantive amendments.
After further consideration and consultation post interview dated 10/16/2025, with mail date 10/21/2025, the 101 rejection was maintained. Applicant argues that the examiner agreed and indicated that the rejection under 101 should be withdrawn. The examiner disagrees with this statement. As noted in interview summary from interview dated 10/16/2025 with mail date 10/21/2025, with respect to the 101 rejection—the examiner agreed that the claimed device parts of a microfluidic unit and a heating and cooling arrangement, an optical or electrochemical reader arrangement, and the concrete method steps of detecting optical or electrochemical signals are not trying to tie up a judicial exception, but from the 101 analysis they still do from how they are instantly claimed--- especially at the level of generality claimed and since the instantly claimed method is drawn towards what it is---“determining a characteristic property of a molecular interaction.”
It is noted though that very broad claims do not necessarily make claims patent-inelligible, the generally and breadth of the claims do certainly play a factor instantly. For example, the instant preamble does not even say what the molecular property is which is “determined,” which is an abstract idea. For example, is the molecular property which is determined, protein folding or unfolding? Even further, again the preamble recites “determining,” which is a mental process/abstract idea, but in the claim, “detecting,” “optical signals or electrochemical signals is recited. Detecting and measuring could be argues more strongly to not be a mental process than the claimed “determining.”
Even further—again though there is nothing rejection wise wrong with using terms in the claim like “optical reader arrangement,” or “heating and/or cooling arrangement,” these terms are so broad in addition to flow through a microfluidic unit, and the equally broad method steps associated with them such as, “ the method comprises reducing velocity,” that they do not help matters.
Therefore, for these reasons and the reasons shown in the 101 rejection which is updated for the claims as amended 10/17/2025, nothing claimed practically applies the abstract idea, at step 2A,2, nor does anything claimed add significantly more at step 2B..
The reasons for this are shown above in the 101 rejection. The examiner has not responded to this here as the claims were amended, so how the amendments are interpreted are shown in the above 101 rejection.
Lastly for the 101 rejection--- the examiner notes again as they did in the last office action, that the specification for the instant invention makes mentioned that the method provides for improved, rapid, and simpler identification of liquid-liquid phase separation systems (PGPub paragraph 0090-0091). The instant specification also shows that the instant method has a computer system which is programmed to improve reading accuracy in a signal that exceeds a preset threshold (paragraph 0224). It is noted that there are many methods and steps which are disclosed with respect to how these improvements take place, but neither the improvement itself, nor all elements leading to the improvement are claimed.
If applicant would like to overcome the 101 rejection, it is suggested that they add more specific details to the claims, and they could consider adding elements/details for how the disclosed improvements are accomplished through either both the claimed or by adding currently unclaimed device parts and method steps to show this.
With respect to the prior art rejection, applicant argues that for Claim 1 & 4 the prior art of PEARSON in view of HASSARD does not teach of making two or more readings as a function of time from multiple fractions in a reading section of a microfluidic unit. The examiner points out that any section of a microfluidic unit can be considered a reading section through broadest reasonable interpretation. Further, HADDAD in view of WEIGL is now used as shown above in addition to PEARSON, instead of HASSARD.
Further for Claims 1 & 4 applicant argues that the prior art of PEARSON in view of HASSARD does not teach of the condition jump comprising subjecting the liquid sample to a jump in temperature from a first temperature to a second temperature wherein the second temperature is homogenous throughout the sample. With respect to this- the examiner points out that HADDAD in view of WEIGL is now used as shown above in addition to PEARSON to teach of this instead of HASSARD.
Further for Claims 1 & 4 applicant argues that the prior art of PEARSON in view of HASSARD does not teach of maintaining the liquid sample at a second temperature during at least part of the time of detection. Again, HADDAD, a new reference is used to show of this as shown in the rejection above.
Applicant further argues about the HASSARD reference. The examiner notes that the HASSARD reference is no longer used. Therefore, applicant’s arguments with respect to the instantly amended claims with respect to HASSARD were convincing and a new grounds of rejection is shown above for the claims amended 10/17/2025.
Applicant argues that the WEIGL reference is incompatible with PEARSONs set up, but does not really state why they think this. Seemingly applicant is arguing that there is no temperature jump so that it is incompatible. The examiner notes that since the other references PEARSON and HADDAD taught of this and a 103 rejection was made, WEIGL is not required to. All used references are relevant to the scope of the instant invention and claims and therefore they are not non-analogous art.
In response to applicant's argument, it has been held that a prior art reference must either be in the field of the inventor' s endeavor or, if not, then be reasonably pertinent to the particular problem with which the inventor was concerned, in order to be relied upon as a basis for rejection of the claimed invention. See In re Oetiker, 977 F.2d 1443, 24 USPQ2d 1443 (Fed. Cir. 1992). All used pieces of prior art are reasonably pertinent to the problems inventor is concerned with, at least as broadly claimed.
Applicant further argues with respect to Claim 15, but it is unclear what applicant is really arguing about with respect to this claim. Applicant argues about Claim 15 for about 2 pages of arguments, but has not added this material to any of the independent claims. It seems that applicant is arguing that YANG does not teach of there being liquid liquid phase separation in a flowing system and instead teaches of a non-flowing system. With respect to this, the examiner notes that a flowing system was already taught in PEARSON and HADDAD so YANG is not required to as a 103 rejection was made. Further, for Claim 1 which Claim 15 depends on through Claim 6, does not require that liquid liquid phase separation is measured or the “characteristic property,” which is actually what is required to be measured in Claim 1.
All claims remain rejected at this time.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA M FRITCHMAN whose telephone number is (303)297-4344. The examiner can normally be reached 9:30-4:30 MT Monday-Friday.
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758