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 Non-Final Office Action based on application 17/910546 RCE filed 08/13/2026. CON 18/669414 is co-pending.
Claims 112, 114-118, 120-124 & 130 have fully considered.
Claims 1-111, 113, 119, & 125-129 are cancelled.
Claims 131-133 are withdrawn.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/13/2026 has been entered.
Double Patenting
The non-statutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A non-statutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 112, 114-118, 120-124 & 130 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19, 22, & 24-28 & 31-34 of copending Application No. 18/669414 in view of 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 (as cited on IDS dated 10/11/2022) in view of HASSARD in US 20050054081 and further in view of YANG in US 20220003661, and WEIGL in US 20020090644.
Application and 18/669414 claims, “a method for determining a characteristic property of a molecular interaction, 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 in said liquid sample, the particle comprises a marker in at least one of its state of equilibrium and state of non-equilibrium; e bringing the particle in a state of non-equilibrium by subjecting the sample to a condition jump; detecting said marker as a function of time during at least a portion of a relaxation time for said particle; and e determining said characteristic property of said molecular interaction, wherein said condition jump comprises subjecting the sample to a jump in temperature from at least one first temperature to a second condition at a second temperature and the method further comprises maintaining said second temperature during at least a part of the time of detecting of said marker.” 18/669414 does not claim, “ a jump time of less than 1 minute,” “detecting an optical signal,” or that the “detecting is performed at a reading rate of at least 5 readings per minute….using an optical reader arrangement or an electrochemical reader arrangement.”
However, KINTES, YANG and WEIGL make these things obvious as shown in the rejections below. It would have in particular been obvious to combine the teachings of KINTES with the 18/669414 to arrive at the instant invention and to study reactions using the timing and device components claimed and as is taught by KINTES due to the advantages this offers for studying reaction kinetics (KINTES, abstract). This is a provisional non-statutory double patenting rejection.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
This application includes one or more claim limitations that do not use the word “means,” but are nonetheless being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, because the claim limitation(s) uses a generic placeholder that is coupled with functional language without reciting sufficient structure to perform the recited function and the generic placeholder is not preceded by a structural modifier.
Such claim limitation(s) is/are:
In Claim 112 and those dependent therefrom:
“optical reader arrangement,”—described in the instant PGPUB specification 0023---- but is not described with particular structures anywhere.
“condition jump arrangement that comprises a heating and/or cooling arrangement,”--- these are described in the instant PGpub paragraphs 0238-0240 as being a blower or resistive or peltier,” heaters.
“computer system to process…”—is interpreted as a physical computer and this is shown instant PGPub paragraph 0230 & 0287.
Because this/these claim limitation(s) is/are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, it/they is/are being interpreted to cover the corresponding structure described in the specification as performing the claimed function, and equivalents thereof.
If applicant does not intend to have this/these limitation(s) interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, applicant may: (1) amend the claim limitation(s) to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph (e.g., by reciting sufficient structure to perform the claimed function); or (2) present a sufficient showing that the claim limitation(s) recite(s) sufficient structure to perform the claimed function so as to avoid it/them being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph.
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 112, 114-118, 120-124 & 130 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: Are the claims directed to a statutory category of invention?
Yes, the claims are drawn towards a statutory category (a method).
Step 2A, Prong 1: Do the claims involve a Judicial Exception?
Independent claim 112 and 115 and those that depend therefrom involve the judicial exception of an abstract idea.
In Claim 112, the method is for, “determining a kinetic parameter,” and in Claim 115 for “determining a folding parameter.” These phrases and concepts are in both the preamble and claim body. “Determining,” as claimed, is mental processes, which is an abstract idea judicial exception. Kinetic parameters and folding parameters---are values derived from experimental data that characterize things such as rate of chemical reaction, or how fast other processes move. This is all math & data analysis or calculations from data and are abstract ideas. See MPEP 2106.04 (a).
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 independent Claim 112, the answer here is no to both questions.
Claim 112 includes the additional steps of:
Providing a liquid sample comprising a particle and a binding partner (that are capable of being in equilibrium or non-equilibrium). This can read on many things. For example, providing a blood sample that contains protein (particle) and antibodies or antibody bound to optical label (binding partner and marker); or a blood sample that contains red blood cells (particle) and hemoglobin/bound to optical label (binding partner).
Bringing the particle into a state of non-equilibrium and subjecting the sample to a condition jump. This is then further limited to that the condition jump occurs in 1 minute or less. This is then further limited to that the condition jump is a temperature jump that is brought on by a “heating or cooling arrangement,” “of an apparatus configured for performing the condition jump..,” and that the second temperature is homogenous throughout the sample.
A “homogenous,” temperature also happens naturally through the laws of thermodynamics. 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 of a marker of the particle as a function of time wherein the detecting is performed by an optical reader arrangement or an electrochemical reader arrangement. Detecting is done during at least a portion of the relaxation time and the liquid sample is not diluted. It is also specified that the reading rate is 5 readings per minute.
The detecting further includes performing two or more readings from different fractions of the liquid as a function of time from different fractions of the sample as the sample is flowing in a reading section of a microfluidic unit, wherein the microfluidic unit is at least partly located in a temperature controlled maintaining compartment. The instant “detecting,” and subjecting to a condition jump by a heating or cooling arrangement is done specifically to use the judicial exception—“determining a kinetic property.” Therefore, the generic detection is done as a data pull/is insignificant extra-solution activity for the claimed judicial exception. (See data gathering – see MPEP 2106.05(g)).
After that in the claim a computer system is provided to process the detected signals for and determining the kinetic parameter of said molecular interaction from the particle/marker the optical signals, however as the computer is not claimed as a specially programmed computer in any way. Even if “configured to,” “or programmed to,” or similar language was added to the claim to indicate programming and a structural change, nothing more specific than “determining the kinetic parameter of the molecular interaction,” is claimed which can be many different things, as claimed- this on using a general computer to perform general math. Math is an abstract idea itself.
Further, all of the claimed, optical measurement and readers and microfluidic units located in a temperature controlled compartment and heating and cool arrangements in apparatus using particles and markers subjected to condition jumps are well understood routine and conventional (WURC) detection devices in the art, as shown by the prior art in the rejection below. Things that are WURC, do not add significantly more to the claims, in a way which overcomes recitation/claiming of a judicial exception. These things also do practically the judicial exception as the measurement related items (optical measurement readers, microfluidic units, heating a cooling arrangements, particles, markers and computers) as claimed are all used for data gathering to accomplish the judicial exceptions, and further, no steps are performed after one determines the kinetic parameter or folding parameter, and therefore there is no practical application.
The examiner notes that all of this is especially true at the level of generality all of the above is claimed at.
This holds true when a microfluidic unit is used to detect a flowing sample and the claimed use of them in making multiple measurements from fractions and the claimed computer making kinetic or folding parameter calculations are also well understood routine and conventional (WURC). Claims 112 requires that the method is performed, “while reducing the risk of degrading the sample.” This is a result of the claimed taking multiple readings from different fractions, however this as claimed is just an intended result. As claimed, what is actually done is the taking of multiple samples and measurements, respectively from different fractions of samples--- which is well understood, routine and conventional. Therefore, this does not add significantly more- nor does it add a technological improvement.
That all of the above is WURC, is evidenced by the PEARSON reference(also used in the art rejection below)-- 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 (as cited on IDS dated 10/11/2022, Page 644, column 2, last paragraph, abstract, pages 644-645 and figure 1, Figure 3, 4, 6).
It is further noted that applicant does not claim a specifically or specially programmed computer. As claimed, the computer element shows no technological improvement and is merely a generic computer. See MPEP 2106.05 (b) that expresses that merely adding a generic computer, generic computer components, or a programmed computer to perform generic computer functions does not overcome eligibility rejections.
Though not claimed-- since applicant is expressing binding, the kinetic parameters could be things such as the rate of association or disassociation, or determination of equilibrium dissociation constants, though this is not claimed.
Even if these things were claimed, it is noted that all of these determinations are done by reading off a chart or graph and performing math. Therefore, this would be considered a generic comparison that can be done by the claimed computer--- therefore is not a practical application and also all of the claimed elements are WURC as shown above so would also not add significantly more.
See MPEP 2106.04(a)(2) III. C. A Claim That Requires a Computer May Still Recite a Mental Process. & further 1. “Performing a mental process on a generic computer.”
Therefore, for all the reasons above, independent claim 112 does not recite significantly more than the abstract idea at step 2B, nor does it integrate the abstract idea into a practical application at step 2A/2.
Claim 115- was amended 08/13/2026 and carries mostly the same analysis as for Claim 112. Claim 115 adds limitations including:
1.That the optical or electrochemical signals are detected during a relaxation time.
This does not change the fact that optical signals and signal detection is routine and conventional in the art as shown and evidenced by the art show for Claim 112 above, and as claimed are being used as a data pull. Therefore this does not add significantly more or practically apply 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. Therefore, this does not add significantly more or practically apply 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).
All proteins have structures which can denature when exposed to high heat. Therefore this is a natural occurrence and therefore does not practically apply or add significantly more to the judicial exception, as it is something that is well understood and routinely happens.
That the temperature controlled maintaining compartment is “configured for maintaining…sample at a second temperature.” With respect to this, the examiner notes that heaters, which maintain temperatures of compartments are WURC, and therefore this does not add significantly more. This is evidenced by the PEARSON reference, again as shown for Claim 112 above, by also in Pearson, Page 644, column 2, last paragraph). (abstract, pages 644-645 and figure 1, Figure 3, 4, 6.
Analysis of the 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 or amount to significantly more?). Here, none of the dependent claims 114, 116-118, 120-124 & 130 integrate the abstract idea into a practical application or add significantly more.
Claim 114 recites more specification on what is meant by the particle 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.
Claim 116 specifies that the conformation (spatial arrangement of constituent atoms) of the protein changes after the condition jump, and further specifies that the marker changes signal based on its conformation change. Again- this is something that routinely and naturally happens to proteins when temperature changes occur. Therefore does not practically apply or add significantly more to the judicial exception.
Claim 117 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 118 specifies that the microfluidic unit and that the microfluidic unit comprises an introduction section that has a cross section of 1 mm or less and that it’s a capillary channel. However as claimed, this is extra solution activity— an uses a routine and conventional device (microfluidic capillary 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 120 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 121 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 122 specifies that the second temperature is from about 5 degrees Celsius (41 Fahrenheit) to about 50 degrees Celsius (122 degrees Fahrenheit). 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 123 specifies that the microfluidic unit comprises an introduction section that is a capillary channel and reading out section and that reading out occurs while sample is flowing through microfluidic device and also the condition jump occurs while the liquid sample is in the device. Microfluidic devices having inlets and analysis section of capillary size 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 124 specifies that reading of consecutive samples happens at different times. Again- the claimed reading is an abstract idea so this does not practically apply or add significantly more to the judicial exception.
Claim 130 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. 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,” to “ensure elected velocity” and that velocity is adjustable--- these limitations do not integrate the judicial exception into a practical application or 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 § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 112, 114-118, 120-124 & 130 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
With respect to Claim 112, the first bullet point claims “the particle and the binding partner are capable of being in a state of equilibrium and a state of non-equilibirum in the liquid sample,” then “the particle comprising a marker in at least one of it’s state of equilibrium or its state of non-equilibrium.” From this, it is not clear it the “its,” is an attempt to refer to the particles state of equilibrium or not. As claimed it is separate, but as the particle comprises the marker this is unclear.
Further with respect to Claim 112, in the first paragraph after the last bullet point, a “homogenous second temperature,” is claimed, however it is unclear what applicant means by this. It is the examiners understanding that the all temperatures are homogenous. Does applicant instead mean that the entire liquid is brought to a second temperature which is homogenous throughout the whole liquid? Further, the claim is unclear since at some times it refers to the “homogenous second temperature,” and at other times, just “the second temperature.” Therefore, it’s unclear if these refer to the same temperature or not.
Further for Claim 112, in the first paragraph after the last bullet, applicant describes, “the entire liquid,” however “entire liquid,” was not referred to priorly in the claim. Therefore, this does not have proper antecedent basis. Then, later in the claim applicant just goes back to referring to it as “the liquid sample,” so it’s unclear if applicant means the entire liquid sample or not. This is unclear.
Further for Claim 112, in the 3rd to last paragraph of the claim, “the microfluidic unit,” fails to have proper antecedent basis. As “microfluidic unit,” was not mentioned prior to this in the claims, it is not clear what “the,” refers back to. Further, in the second to last paragraph of the claim, “a microfluidic unit,” is used and it is unclear of this means the same microfluidic unit previously mentioned as “the ,” is not used.
Further with respect to Claim 112, it is unclear if the “temperature controlled heating and/or cooling arrangement of an apparatus,” and the “temperature controlled maintaining part of the apparatus,” are the same structures or not. Heating or cooling to a certain temperature that is then maintained in any compartment can be considered to be both of these structures.
Even further with respect to Claim 112, last paragraph, “the optical signals,” fail to have proper antecedent basis as “optical signals,” were not referred to priorly in the claim and instead only “optically readable markers,” are claimed.
The above issues present in Claim 112 are also present in independent Claim 115 and also have an effect on the dependent claims, so when applicant corrects in the independent Claims 112& 115, they should make sure the dependent claims read properly as well as have proper antecedent basis to the terms used in Claim 112.
Further with respect to Claims 112 & 115, recited “while reducing the risk of degrading,” is a relative phrase as is risk reduction. What one would consider a reduced risk, another might not. Therefore, “reducing,” and “degrading,” are relative terms and not defined in the claims and the claims are therefore unclear.
Claim 114 is unclear as it states that “at least one of the particle or the binding partner comprises the markers,” however claim 112 already requires that “the particle comprising a marker.” Therefore, claim 114 seems to be improperly broadening claim 112, and is therefore unclear.
Claim 130 states “a microfluidic unit,” which was already mentioned in Claim 112 from which it depends on. Therefore, it fails to have proper antecedent basis, is unclear, and requires correction.
Claims 112 and 115 claim an “optical reader arrangement.” This has been interpreted under 112 f as shown above, but the specification does not show sufficient structure for this term and therefore it is unclear what is meant by it.
Claims 114, 116-118, 120-124 & 130 are also rejected by virtue of their dependency on Claims 112 and 115.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 112 & 115 and those dependent therefrom are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim limitation “optical reader arrangement” om Claims 112 & 115 invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. However, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function. Therefore, the claim does not have proper written description and is rejected under 35 U.S.C. 112(a).
Applicant may:
(a) Amend the claim so that the claim limitation will no longer be interpreted as a limitation under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
(b) Amend the written description of the specification such that it expressly recites what structure, material, or acts perform the entire claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(c) Amend the written description of the specification such that it clearly links the structure, material, or acts disclosed therein to the function recited in the claim, without introducing any new matter (35 U.S.C. 132(a)).
If applicant is of the opinion that the written description of the specification already implicitly or inherently discloses the corresponding structure, material, or acts and clearly links them to the function so that one of ordinary skill in the art would recognize what structure, material, or acts perform the claimed function, applicant should clarify the record by either:
(a) Amending the written description of the specification such that it expressly recites the corresponding structure, material, or acts for performing the claimed function and clearly links or associates the structure, material, or acts to the claimed function, without introducing any new matter (35 U.S.C. 132(a)); or
(b) Stating on the record what the corresponding structure, material, or acts, which are implicitly or inherently set forth in the written description of the specification, perform the claimed function. For more information, see 37 CFR 1.75(d) and MPEP §§ 608.01(o) and 2181.
Claims 114, 116-118, 120-124 & 130 are also rejected by virtue of their dependency on Claims 112 & 115.
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 112, 114-118, 120-122 & 130 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 (as cited on IDS dated 10/11/2022) in view of HASSARD in US 20050054081 and further in view of YANG in US 20220003661.
With respect to Claims 112 & 115, 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). PEARSON teaches that the method is used for determination of relaxation kinetics and kinetic data (kinetic parameters) and protein folding (folding parameter) (abstract, Page 649, column 2, paragraph 1, line 2 and paragraph 2, line 17), 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- which is optically readable as claimed)(Page 644, column 2, figure 1 & description & Figure 2 and description), in a solvent (the buffer in PEARSON can be considered to be the claimed solvent, Page 644, column 1, paragraph 7).
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), and
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--- each line of graph can be considered to be a different fraction,), 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).
As claimed, “while reducing the risk of degrading the sample.” This is a result of the claimed taking multiple readings from different fractions---so the instant prior art teaching would result in this intended result, since it teaches of the process step as claimed.
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) 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.
PEARSON further teaches 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 further teaches of using a computer to collect and analyze the collected data (Page 644, column 2, last paragraph).
If the condition jump being a temperature jump and specifically the temperature heating arrangement (creating a temperature) and microfluidic unit being in a temperature controlled unit, is unclear to one of ordinary skill in the art from PEARSON, HASSARD is used to remedy this.
HASSARD teaches a method for analyzing temperature-dependent molecular configurations such as folding that comprises a multi-channel flow-through chip (12) along which molecules to be analyzed pass. A temperature gradient (which leads to homogenous temperature through the laws of thermodynamics) is maintained along the length of the chip. As molecules pass along the channels they fold or unfold, in response to the changing temperature (abstract). The channels are temperature controlled so are a microfluidic unit located at least partly in a temperature controlled maintaining unit (paragraph 0039, 0037), as instantly claimed. HASSARD further teaches of using protein samples (paragraph 0051, 0016, 0019) and that the sample (protein-liquid since it flows) contained in a buffer (paragraph 0036—so the proteins are contained in the same non-diluted way as instantly disclosed by applicant meaning in a buffer), flows through the chip/channel (abstract). HASSARD teaches that they use heating elements along the chip (heating arrangements) (paragraph 0013).
It would have been obvious to one of ordinary skill in the art to use a temperature jump as the condition jump and a heating arrangement as is done in HASSARD in the method of PEARSON before the effective filing date of the instant invention due to flow through method as is done in HASSARD due the affect temperature has on protein folding and unfolding advantage this would offer for studying protein folding and unfolding which will understanding of protein folding and stability will provide a clearer insight into the causes of disease, and therefore will allow the development of better treatments or preventative measures for disease. (HASSARD, paragraphs 0004-0006).
PEARSON and HASSARD does not specifically call out that the jump takes 1 minute. They also do not call out making 5 readings per minute.
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). YANG also 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 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 HASSARD due to the advantage this has for giving information for reaction kinetic study (YANG, paragraph 0048) and due to the advantage it has for studying temperature dependent reaction kinetics (paragraph 0082).
With respect to Claim 114, see Claim 1 rejection for PEARSON. PEARSON further teaches of using the apparatus and method of claim 1 to study protein folding (protein folding structure changes happen at changes in temperature) (Page 649, column 2, paragraph 2).
With respect to Claim 116, see Claim 1 rejection for PEARSON. PEARSON further teaches of using the apparatus and method of claim 1 to study protein folding (protein folding structure changes happen at changes in temperature) (Page 649, column 2, paragraph 2). 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) 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).
With respect to Claim 117, PEARSON teaches 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) 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.
With respect to Claim 118, PEARSON teaches of the claim as shown above for Claim 117 and further teaches of the inlet being an introduction section. PEARSON does 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 to use the capillaries the size used in YANG in the method of DUHR due to the advantage this has as being a readily available (VitroCom) capillary (paragraph 0182).
With respect to Claim 120, PEARSON and HASSARD teaches of the claimed invention, but 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 to control the temperature by fill level as is done in YANG in the method of PEARSON and HASSARD due to the advantage this has for controlling reaction kinetics (YANG, paragraph 0156).
With respect to Claim 121, PEARSON teaches of the invention as shown above, but does not teach of a temperature jump of 2 degrees Celsius. HASSARD teaches that the temperature across the gradient will depend upon the nature of the protein being analyzed, and may be adjusted according to the type of protein, and/or to the degree of folding or unfolding which is desired. Typically, the temperature range will be in the region of 20 degree. C. to 200.degree. C. The exact range for any particular molecule may be readily determined using techniques available in the art (paragraph 0020). See reason for combination from claim 112.
With respect to Claim 122, PEARSON teaches of the invention as shown above, but does not teach of a temperature jump of 2 degrees Celsius. HASSARD teaches that the temperature across the gradient will depend upon the nature of the protein being analyzed, and may be adjusted according to the type of protein, and/or to the degree of folding or unfolding which is desired. Typically, the temperature range will be in the region of 20 degree. C. to 200.degree. C. The exact range for any particular molecule may be readily determined using techniques available in the art (paragraph 0020). See reason for combination from claim 112.
With respect to Claim 130, PEARSON and HASSARD teach of the invention as shown above. They do not teach of the temperature jump being performed in the channel of the microfluidic device.
YANG is used to remedy this and teaches of the invention as shown above for claim 15 and further teaches of doing the temperature jump experiments in a channel (paragraph 0049, 0171, 0037). It would have been obvious to one of ordinary skill in the art to perform the method in the channel of the microfluidic device as is done in YANG in the primary references and one would have had reasonable expectation of success due to the advantage this offers for single experiment/device simplicity purposes (YANG, paragraph 0049, 0004).
Claims 113 & 123-124 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 HASSARD in US 20050054081in view of YANG in US 20220003661 in view of WEIGL in US 20020090644.
With respect to Claims 113 & 124, PEARSON and HASSARD and YANG teach 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 to use sample aliquots or fractions as is done in WEIGL in the method of PEARSON, HASSARD, and YANG due to the advantage this offers in comparing a profile of streams or samples (WEIGL, paragraph 0052).
With respect to Claim 123, PEARSON teaches of the claim as shown above for Claim 112 and 117 and further teaches of the inlet being an introduction section. PEARSON does 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 to use the capillaries the size used in YANG in the method of DUHR due to the advantage this has as being a readily available (VitroCom) capillary (paragraph 0182).
Since YANG does not teach of making readings for multiple fractions, 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 to use sample aliquots or fractions and monitor over time as is done in WEIGL in the method of PEARSON, HASSARD, and YANG due to the advantage this offers in comparing a profile of streams or samples (WEIGL, paragraph 0052).
Response to Arguments
Applicant's arguments filed 08/13/2026 have been fully considered but they are not persuasive.
The double patenting rejection is maintained. Applicant has made not arguments about it presently, other that reciting that the time for filing a terminal disclaimer has not come yet. Therefore, the rejection is maintained.
112, 2nd rejections are shown above. Amendments dated 08/13/2026 did not solve all clarity issues with the claims.
With respect to the 101 rejection, it is maintained. The examiner has reviewed the Subject Matter Eligibility Declaration dated 08/13/2026 by Henrik Jensen. Though this Declaration was informative, it is not found convincing in overcoming the 101 rejection, especially in light of what is claimed. Since applicant’s arguments with respect to the 101 and the Subject Matter Eligibility Declaration greatly overlap in scope, they have been addressed together. The examiner notes that they have consulted with their SPE on the 101 rejection.
Applicant argues with respect to the 101 rejection, that the examiners characterization of the claimed “determining,” as an abstract idea and the remaining limitations as data gathering extra-solution activity and WURC activity is inconsistent with the technical disclosure as a whole. Applicant states that the claimed method for determining a kinetic parameter between a binding partner and particle and determining a folding parameter are instead “quantitative physiochemical measurement results obtained by performing a controlled physical assay on a liquid sample.”
The examiner disagrees. While applicant seems to focus their arguments to this effect on that the claims require optical detection and processing of optical signals, among other things including temperature jumps, the examiner notes that the instant claims themselves are still drawn towards abstract ideas in the claim preambles.
Though the preambles are not always limiting for claims, how the instant claim preambles are recited, certainly plays into why the claims are rejected under 101 instantly. The examiner notes that the claims are not drawn towards a method for detecting optical signals by UV-Vis spectroscopy or anything like that. Instead, as claimed the claims are drawn towards “determining,” in the preamble, and then within the claim body “optical signals,” are detected, however they are not claimed with any detail or specificity. Therefore, at the level of generality claimed, even detection of optical signals, could be read through broadest reasonable interpretation as visually detecting optical signals or color changes, which would still receive a 101 rejection.
In response to applicants arguments, the examiner notes that they do not think that the claim,” merely recites,” determining a parameter. Instead, the claims recite this, without adding sufficient additional limitations to show that significantly more is claimed, or that there is a practical application. Again, the very general nature in which all claim elements are claimed, plays into this determination.
Applicant argues that, “there is no prohibition against a determining step,” as claimed as the last step of a method claim. The examiner overall agrees with this statement. Applicant attempts to further their argument by stating, “that is a determining steps as the last step of a method claim does not somehow doom the claim under USC 101 when the claim as a whole provides a practical improvement.” Again, the examiner agrees that a determining step does not in itself “doom,” a claim, however maintains that for the instant claims it does in fact play into the determination that the claims should be properly rejected under 101. This is due to many things, but likely mostly due to the level of generality of all the claimed elements, in addition to these determining steps. Further, the examiner notes that especially at the level of generality claimed--- not technical improvement is found/seen in these claims.
Applicant argues that the instant claims and the subject matter eligibility declaration are found to shown technical improvements. The examiner disagrees.
Applicant further seems to argues that the important technical features common to Claims 112 & 115 are:
(a) bringing the particle into a state of non-equilibrium by subjecting the liquid sample to a condition jump with a jump time of 1 minute or less; combined with:
(b) wherein the condition jump comprises subjecting the entire liquid sample to a jump in temperature from at least one first temperature to a homogeneous second temperature within the jump time, wherein the particle is brought into the state of non-equilibrium in the liquid sample at the second temperature, and wherein the jump in temperature is provided such that the second temperature is a homogeneous second temperature in the entire liquid sample by using a condition jump arrangement that comprises a heating and/or cooling arrangement configured for performing the condition jump from the at least one first temperature to the second temperature.
Applicant further notes that they view a) and b) above as “controlled physical perturbation,” of the sample and not a mental or mathematical step. With respect to this the examiner agrees that these particular steps are not purely mental or mathematical, but again maintains that the determining a kinetic parameter and determining a folding parameter still are, and the steps applicant argues here are found to not practically apply or add significantly more.
The examiner points out further with respect to the above, none of this shows technological improvement. The test is not whether anything “technical,” is in the claims or not, which is what applicant seems to allude to. Instead, it is do the claims either claim or necessarily effect technological improvement. The examiner again notes, that especially as all of the elements recited in a) and b) above are very general device parts and method steps, no technological improvement is seen.
Applicant seems thus far un-wiling to add any specific detail to claims which could allow them to overcome these matters. Though the examiner does not know if applicant has disclosure for any of this in the specification nor exactly what would result in the instant claims overcoming the 101 rejection, applicant could consider claiming things like what exact folding parameter is detected, what type of optical instrumentation is used for detection and what wavelengths are detected, what exactly the heating a cooling arrangement is device wise (for example is a heating block used, is a lamp used, or oven?), and even further what exactly the particles are and markers are (for example are the markers fluorescent? Are the particles the analyte or are they something like silica beads?).
Applicant further argues that the claimed temperature jump is not merely a preliminary data gathering step, but instead creates the non-equilibirum state whose relaxation is measured. Applicant also emphasizes that the temperature jump is rapid and that the time dependent relaxation signal from which the kinetic or folding parameter is determined would not be produced in the claimed matter without this. With respect to this, the examiner then suggests if this is true, then applicant should claim more specifics with respect to what they mean here.
For example, what is the temperature jump specifically (from what to what?), what relaxation time is used and when are successive measurements taken? And how are these signals then used for determination of the kinetic or folding parameter? None of the specifics for any of this is claimed. The examiner notes though that even if this kind of detail was added to the instant claims, they seem like they might focus on mostly signal processing and still be unpatentable in light of 101, however the examiner cannot determine this at the current time.
Applicant further argues about the claimed homogenous temperatures and that it is “technically significant,” and shows technological improvement as it contributes to reliability of the time dependent measurements. With respect to this, if this is in fact a technological improvement, applicant has not made it clear in the claims how one would ensure homogenous temperatures or heating. All that is claimed currently are very very general heating (heating or cooling arrangement) and processing (computer) parts, with none of the claimed parts really showing any bearance on the purported technological improvement. The examiner notes that if there really is technical improvement, the examiner in the very least needs to be able to clearly see how what is claimed is responsible for it, which is currently not the case. The examiner further notes that there are 112 rejections with respect to this as shown above, so has no further comment on this limitation until/if the claims are cleared up.
Applicant further argues that the instantly claimed optical detection is not just a data pull or insignificant extra solution activity, and that optical signals are not generic data. Applicant instead argues that they optical signals are a specific technical readout of the relaxation process induced by the claimed rapid temperature jump. With respect to this, as claimed the examiner disagrees, though does understand that applicants intentions are different. However, in light of 101 law as all applicant has claimed doing is yes, taking these optical signals and then providing a computer system that determines the folding is kinetic parameter, as currently claimed are interpreted as a data pull for the last step in the claim of “determining,” the kinetic or folding parameter which again is done by math and is a judicial exception.
Applicant further argues that the instant method “reduces degradation of sample or marker.” With respect to this, the examiner notes that there is a 112 clarity issue with respect to this as shown above, so the examiner has no further comment on this until the claims are cleared up.
Applicant further argues that the claims do not “preempt kinetic parameters, folding parameters, molecular interactions, protein folding,” as claimed. Applicant further argues that the instant claims are not directed to, “ a result divorced from a technical process,” and that the Expert Declaration dated 08/13/2026 emphasizes this in that the temperature jump and relaxation measurements are controlled physical perturbations. The examiner disagrees, especially again as in light of the guidance given on what indicates a practical application and significantly more with respect to U.S. 101 law, there is no real practical application claimed, nor is anything significantly more. The examiner again notes, that if applicant thinks the instant process is so controlled, then why not add more detail to the claims with respect to how it is controlled and by what devices and to what temperatures.
Applicant notes that, “the Declaration should be considered as part of the evidentiary record,” and that the Declaration provides “factual evidence,” however does not allude to what they find it “factual,” for. With respect to this, examiner notes that the Declaration has been considered, however maintains that it is not convincing in overcoming the 101 rejection.
Since items VI and VII of the Declaration are not thoroughly discussed in applicants arguments, the examiners also respond to those here.
With respect to Declaration dated 08/13/2026, item VI, applicant argues that the claimed homogenous temperature jump provides a technical improvement. Applicant notably states that this improves reliability and interpretability of the time dependent optical signal, however the examiner notes that there is nothing in the claim showing anything about these supposed improvements. For example, how would one know the optical signal is improved and more interpretable? Compared to what? The examiner further notes that there are 112 issues with respect to the claiming of a homogenous temperature jump and that if any “improvement,” was claimed that there might possible be 112 issues with respect to this as well, since it is a relative term.
Further with respect to Declaration dated 08/13/2026, item VII, applicant argues that the instant kinetic and folding parameters have a relationship to drug development and material science. With respect to this, while the examiner does not doubt this, nothing about this is claimed. In U.S. patent practice, patentability determinations are made based off of what is claimed, and therefore if there are any arguments with respect to this, they are not commensurate in scope with the instant claims.
All pending claims remain rejected under 101.
With respect to the 103 rejection, the rejection is maintained and applicant’s arguments are not convincing. The examiner notes that if applicant is able to add sufficient detail to the claims to overcome the 101 rejection, then it will be easier to overcome the 101 rejection as well. There are also significant 112, clarity issues as shown above which would need overcome as well. This has not been done yet.
With respect to PEARSON, applicant argues that PEARSON teaches of a pressure jump and not a temperature jump (from a first to second temperature). With respect to this, the examiner notes a secondary reference was used to teach of the temperature jump and a 103 rejection was made, so PEARSON does not need to teach of all things which are claimed.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Applicant further argues that PEARSON does not teach of the claimed, reading out as a function of time from multiple fractions. The examiner disagrees and maintains that the claimed language can be interpreted more broadly than applicant argues. The examiner notes that PEARSON does teach of this reading out as a function of time from multiple fractions (abstract, pages 644-645 and figure 1, Figure 3, 4, 6) which would further be capable of the claimed result, “while reducing the risk of degrading the sample.” This is a result of the claimed taking multiple readings from different fractions---so the instant prior art teaching would result in this intended result, since it teaches of the process step as claimed.
Applicant further argues that PEARSON does not teach of flowing a sample in a channel during an optical readout. With respect to this, the examiner notes that this was why the YANG reference was used.
Specifically, YANG teaches of doing the temperature jump experiments in a channel (paragraph 0049, 0171, 0037) and further of making optical measurements (paragraph 0144).
Even further with respect to PEARSON, applicant argues that PEARSON teaches a “different solution to photobleaching,” than the present claims. With respect to this, the examiner notes that this argument is not commensurate in scope with the instant claims as nothing about photobleaching is claimed.
Applicant even further argues that the unit in PEARSON is not a microfluidic unit. Applicant admits though that PEARSON teaches of an optical pressure chamber of 50ul, but that this does not make it a microfluidic unit. The examiner disagrees and maintains that since PEARSON teaches of a chamber for handling micro amounts of fluids, it can be considered a microfluidic unit through broadest reasonable interpretation. If applicant means something different, or more specific, then they should claim it.
Applicant further argues that PEARSON does not detect a change in conformation as a result of a pressure jump. The examiner disagrees. See the rejection of PEARSON as shown above. Applicant seemingly argues this since they think PEARSON relies of theoretical discussion in PEARSON. With respect to this, even if this is the case, this is still a teaching that makes applicants instant invention obvious as shown above.
With respect to the HASSARD reference applicant argues that the HASSARD reference would not cure the deficiencies in PEARSON and applicant further argues that HASSARDS maintaining of a temperature gradient along the length of a chip does not maintain a second temperature as claimed. The examiner disagrees—as the gradient is maintained along the length of the chip, the part of the length of the chip that is at the second temperature will be maintained at the second temperature throughout the maintaining of the temperature gradient.
Applicant argues that the heating strips used in HASSARD would introduce errors and lead to incorrect determinations and that and that in HASSARD the molecules fold or unfold dynamically as they pass along the channel and therefore no equilibrium stage is determined or “capable of,” being determined and therefore is fundamentally different from what is claimed since they argue HASSARD doesn’t teach of the claimed relaxation based determination.
With respect to this, the examiner notes that this is not exactly what is claimed, “Determining an equilibrium stage.” Instead, what is claimed is that the particle and binding partner are capable of being in equilibrium and non equilibrium and further that the particle is brought into a stage of non-equilibirum (where unfolding occurs in the case of protein folding when exposed to high temperature). The temperature gradient in HASSARD is capable of this, and does in fact perform this step, albeit probably in a less direct from point A directly to point D method, and since a gradient is used in HASSARD the folding to unfolding can include for example points A, B, C, and then D for example. The instant claims does not have any language which prevent this stepwise movement of folding from occurring. Further, the examiner again notes, that a 103 rejection was made and PEARSON already taught of the claimed relaxation time as shown above (see figure 4).
With respect to the YANG reference, applicant argues that YANG does not teach of a temperature jump relaxation assay nor starting the reading before the system is stabilized.
With respect to this, the examiner notes that YANG does teach of a temperature jump ( a gradient includes a temperature jump), and further the examiner notes that the claim does not require starting, “the reading before the system is stabilized.”
Specifically, YANG 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). YANG also teaches of making continuous measurements ( so more than 5 readings per minute (paragraph 0048, 0170 Figure 32, 0082).
Applicant further argues that they do not think that YANG teaches of things they already argued that PEARSON and HASSARD do not teach of. The examiner notes that YANG was used to teach of making condition jump of 1 minute or less and also of making five readings/continuous measurements.
Specifically, YANG 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). YANG also 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 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 HASSARD due to the advantage this has for giving information for reaction kinetic study (YANG, paragraph 0048) and due to the advantage it has for studying temperature dependent reaction kinetics (paragraph 0082).
Applicant further argues that the pieces of prior art are incompatible with each other(for example combining a pressure jump and temperature jump system). In response to applicant's arguments, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). Please see the reasons for combination cited in the 103 rejection above.
Applicant further argues that the examiner has impermissibly used the claimed invention as an instruction manual to selectively piece together the prior art. The examiner disagrees with this and in response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). This is the case in the instant claims that the examiner has only used knowledge within the level of one of ordinary skill, so the combination of art is permissible.
In response to applicant's argument that the three pieces of prior art, Pearson, Hassard, and Yang are materially different from eachother/ nonanalogous art, 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). In this case, all pieces of prior art which are reasonably pertinent to the particular problem as claimed of determining kinetic parameters of molecular interactions, especially as broadly claimed. If applicant adds more specific detail to the claims, then this might no longer be the case.
All claims remain rejected.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
BAASKE in US 20170361326.
BAASKE teaches of methods and systems are in particular suitable for experiments with respect to folding and unfolding of proteins and the examination of the stability of biomolecules like proteins. Here, the structure of the biomolecule to be examined, in particular protein or protein complex, is changed by addition of suitable chemicals, for example chaotrops as urea or guanidine hydrochloride or organic solvents, or by change of the temperature (i.e. for example “melting” by increasing the temperature). The secondary and tertiary structure of biomolecules as proteins and nucleic acids is often also dependent on the presence of ligands or cofactors like ions (for example Mg.sup.2+ or Ca.sup.2±). This may be effected for example by measuring the fluorescence (preferably tryptophan fluorescence in case of proteins) under different concentrations of the ligands and/or cofactors.
The biomolecule, preferably protein, may be denatured chemically or thermally, and structural amendments may be measured by intrinsic fluorescence (preferably tryptophan fluorescence in case of proteins). There, for example changes in the fluorescence intensity or shifting of fluorescence maxima may be detected. The melting point of the biomolecule to be examined, for example protein, may also be determined. The melting point is the state in which one half of the biomolecule to be examined, for example protein, is folded and the other half is unfolded. In case proteins are examined, for example the tryptophan fluorescence at a wavelength of 330 nm and/or 350 nm can be measured. Here, the change of the intensity of the fluorescence, for example dependent on the temperature or on the addition of a denaturant or cofactor/ligand may be determined and/or a periodical process may be recorded. The quotient of the fluorescence intensity at 330 nm to the fluorescence intensity at 350 nm (F330/F350) is a preferred indicator. For example, the melting point may be determined from the maximum of the first derivative of the F330/F350 curve (paragraphs 0038-0039).
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/REBECCA M FRITCHMAN/Primary Examiner, Art Unit 1758
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