DETAILED ACTION
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 .
Claim Status
Claims 1-24 are currently pending and under exam herein.
Claims 1-24 are rejected.
Priority
The instant application is a National Stage Application under 35 U.S.C. 371 of co-pending PCT application PCT/IB21/61322 filed 3 December 2021, which claims the benefit of U.S. Provisional Application No. 63/123,170 filed 9 December 2020. Benefit is acknowledged. At this point in examination, the effective filing date of claims 1-24 is 9 December 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 1 May 2025 complies with 37 CFR 1.98. Accordingly, all references listed have been considered by the examiner.
The IDS filed 5 August 2024 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. Specifically, the copy of the non-patent literature reference by Wicke titled “Empirische und theoretische Untersuchungen der Sorptionsgeschwindigkeit von Gasen an porosen Stoffen II” was provided in a foreign language with no English translation. Thus, this reference has been lined through on the IDS and has not been considered. All other references have been considered.
Drawings
The drawings filed on 25 May 2023 have been received and are accepted.
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 1-24 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. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999).
The term “chromatography machine” in claim 1 is used by the claim to mean “a chromatography machine including a first dispersed plug flow reactor (DPFR) and a continuous stirred tank reactor (CSTR) prior to a column, and a second DPFR after the column.” The accepted meaning of the term “chromatography machine” is the physical laboratory instrument used to separate, identify, and purify the various individual components within a complex mixture. See Geoffrey Green, Types of Chromatography Machines and Common Applications, MISUMI Mech Lab Blog §§ What is Chromatography? para.1 & Common Chromatography Machine Components paras.1-3 (25 July 2023). DPFRs and CSTRs are not physical parts of a machine, but are instead mathematical building blocks used in computer models to simulate fluid flow and extra-column band broadening in liquid chromatography systems. See Wikipedia, Continuous stirred-tank reactor, para.1 https://en.wikipedia.org/wiki/Continuous_stirred-tank_reactor (last visited 14 August 2026); and Borosil Scientific, What Is a Plug Flow Reactor?, para.1 https://www.borosilscientific.com/what-is-a-plug-flow-reactor/ (last visited 14 August 2026). This renders the term “chromatography machine” indefinite because the specification does not clearly redefine the term. Therefore, claim 1 is rejected under 35 U.S.C. 112(b) because the metes and bounds of the claim is unclear. Claims 2-24 are similarly rejected due to their dependency on claim 1.
For purposes of the present examination, the term “chromatography machine” will be interpreted to mean a mathematical and mechanistic model of a chromatography system, rather than a physical laboratory instrument.
Claim 9, which depends on claim 1, recites the limitation “the first DPFR and a CSTR prior to the column” in line 1. Claim 1 recites a first DPFR and a CSTR prior to a column in the first limitation, which are referred to as “the first DPFR and the CSTR” in the last limitation. The recitation of “a CSTR prior to the column” in claim 9 renders the claim indefinite because it is unclear whether claim 9 is referring to the CSTR of claim 1 or a separate CSTR prior to the column. Therefore, claim 9 is rejected under 35 U.S.C. 112(b) because the metes and bounds of the claim is unclear.
Claim 12, which depends on claim 1, recites the limitation “the transport model parameters” in line 1. Claim 1 recites “transport model parameters for a transport model associated with the second DPFR” and “transport model parameters for a transport model associated with the first DPFR and the CSTR.” The recitation of “the transport model parameters” in claim 12 renders the claim indefinite because it is unclear whether claim 12 is referring to the transport model parameters for a transport model associated with the second DPFR or the first DPFR and the CSTR. Therefore, claim 12 is rejected under 35 U.S.C. 112(b) because the metes and bounds of the claim is unclear.
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 of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (abstract ideas) without significantly more. Under MPEP § 2106, subject matter is patent eligible when the claimed invention is to one of the four statutory categories of invention [Step 1], and the claim is not directed to a judicial exception [Step 2A] unless the claim as a whole includes additional limitations amounting to significantly more than the exception [Step 2B].
Step 1
Claims 1-24 describe inventions that are to one of the statutory categories. In Step 1, a claim must fall within one of the four enumerated categories of statutory subject matter (process, machine, manufacture, or composition of matter); a claim falling outside these categories is ineligible without further analysis. See MPEP § 2106.03. Claims 1-22 are properly to one of the four statutory categories because the claimed invention is a method, which falls into the process category [Step 1: Yes]. Claim 23 is properly to one of the four statutory categories because the claimed invention is a system, which falls into the machine category [Step 1: Yes]. Claim 24 is properly to one of the four statutory categories because the claimed invention is a non-transitory computer-readable storage medium storing instructions, which falls into the manufacture category [Step 1: Yes].
Step 2A
Under Step 2A, a claim is directed to a judicial exception if, under the broadest reasonable interpretation, it recites an abstract idea, law of nature, or natural phenomena [Prong One] without the claim as a whole integrating the exception into a practical application [Prong Two]. Abstract ideas include mathematical concepts, mental processes, and certain methods of organizing human activity. Mathematical concepts encompass mathematical relationships, formulas, equations, and mathematical calculations. See MPEP § 2106.04(a)(2)(I). Mental processes involve concepts that can be performed in the human mind or by a human with the aid of pen and paper, such as observations, evaluations, judgments, or opinions. See MPEP § 2106.04(a)(2)(III). Certain methods of organizing human activity include fundamental economic principles, commercial or legal interactions, and managing personal behavior or relationships. See MPEP § 2106.04(a)(2)(II). Laws of nature and natural phenomena, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature. See MPEP § 2106.04(b)-(c).
Prong One
A claim recites a judicial exception when it sets forth or describes a law of nature, natural phenomenon, or abstract idea. Claims 1-24 recite abstract ideas that fall into the groupings of mathematical concepts and mental processes.
Claim 1 recites the following limitations, which describe abstract ideas within the mathematical concepts and/or mental processes groupings:
obtaining, for a chromatography machine including a first dispersed plug flow reactor (DPFR) and a continuous stirred tank reactor (CSTR) prior to a column, and a second DPFR after the column, geometric measurements associated with the second DPFR;
generating, by a processor, transport model parameters for a transport model associated with the second DPFR based on the geometric measurements;
feeding a tracer molecule into the chromatography machine;
capturing one or more tracer molecule measurements based on the tracer molecule traveling through the chromatography machine; and
estimating, by the processor, based on the transport model associated with the second DPFR and the one or more tracer molecule measurements based on the tracer molecule traveling through the chromatography machine, one or more transport model parameters for a transport model associated with the first DPFR and the CSTR.
The limitation of obtaining geometric measurements involves assigning or selecting numerical geometric values that define parameters of the mathematical DPFR model component, which constitutes an abstract idea within the mathematical concepts and mental processes groupings. The limitation of generating transport model parameters involves calculating model parameters from geometric inputs using the mathematical equations of a DPFR, which constitutes an abstract idea within the mathematical concepts grouping. The limitation of feeding a tracer molecule into the chromatography machine involves simulating the introduction of a tracer or defining initial conditions for a tracer species inside the mathematical model, which constitutes an abstract idea within the mathematical concepts and mental processes groupings. The limitation of capturing tracer molecule measurements involves computing and recording the simulated output of the mathematical model, which constitutes an abstract idea within the mathematical concepts grouping. The limitation of estimating transport model parameters involves inverse parameter estimation/optimization that adjusts the remaining model parameters, which constitutes an abstract idea within the mathematical concepts grouping.
Claim 2 recites the following limitations, which describe abstract ideas within the mathematical concepts and/or mental processes groupings:
feeding an experimental sample into the chromatography machine;
capturing one or more experimental measurements based on the experimental sample traveling through the chromatography machine; and
estimating, by the processor, based on the one or more experimental measurements based on the experimental sample traveling through the chromatography machine, the estimated one or more transport model parameters for the transport model associated with the first DPFR and the CSTR, and the transport parameters for the transport model associated with the second DPFR, one or more adsorption model parameters for an adsorption model associated with the experimental sample.
The limitation of feeding an experimental sample into the chromatography machine involves simulating introduction of a sample species into the mathematical model or defining input conditions for a sample species in the mathematical model, which constitutes an abstract idea within the mathematical concepts and mental processes groupings. The limitation of capturing experimental measurements involves computing and recording the corresponding simulated output chromatogram, which constitutes an abstract idea within the mathematical concepts grouping. The limitation of estimating adsorption model parameters involves fitting isotherm parameters by inverse methods, which constitutes an abstract idea within the mathematical concepts grouping.
Claims 3-22 recite the following limitations, which describe or narrow abstract ideas:
Claim 3 recites wherein the geometric measurements include tubing diameter measurements and tubing length measurements associated with the second DPFR.
Claim 4 recites wherein the one or more tracer molecule measurements are captured based on a chromatogram associated with the tracer molecule traveling through the chromatography machine.
Claim 5 recites the one or more experimental measurements are captured based on a chromatogram associated with the experimental sample traveling through the chromatography machine.
Claim 6 recites identifying, by the processor, the experimental sample based on the adsorption model associated with the experimental sample.
Claim 7 recites wherein the estimating the one or more adsorption model parameters for the adsorption model associated with the experimental sample is a first estimating of a first one or more adsorption parameters for a first adsorption model associated with the experimental sample, and further comprising: a second estimating, by the processor, of a second one or more adsorption parameters for a second adsorption model associated with the experimental sample based on a range associated with the first one or more binding parameters for the first adsorption model associated with the experimental sample.
Claim 8 recites identifying, by the processor, the experimental sample based on the second adsorption model associated with the experimental sample.
Claim 9 recites wherein the first DPFR and a CSTR prior to the column, and the second DPFR after the column are part of an inlet flow path of the chromatography machine, and wherein the chromatography machine further includes a sample flow path having a first DPFR and a CSTR prior to a sample flow path column, and a second DPFR after the sample flow path column, and wherein the steps of claim 1 are further performed for the first DPFR and the CSTR prior to the sample flow path column, and the second DPFR after the sample flow path column.
Claim 10 recites wherein the experimental sample is a first experimental sample, and further comprising: feeding a second experimental sample into the chromatography machine; capturing one or more second experimental measurements based on the second experimental sample traveling through the chromatography machine; and estimating, by the processor, based on the one or more second experimental measurements based on the second experimental sample traveling through the chromatography machine, the estimated one or more transport model parameters for the transport model associated with the first DPFR and the CSTR, and the transport parameters for the transport model associated with the second DPFR, one or more adsorption model parameters for an adsorption model associated with the second experimental sample.
Claim 11 recites wherein the second experimental sample is distinct from the first experimental sample.
Claim 12 recites wherein the transport model parameters include one or more of: dispersion coefficient in DPFR, volume of DPFR, cross-section area of DPFR, and volume of CSTR.
Claim 13 recites wherein the adsorption model parameters include one or more of: adsorption coefficient, desorption coefficient, characteristic charge, and shielding factor.
Claim 14 recites estimating, by the processor, based on the transport model associated with the first DPFR and the CSTR, the transport model associated with the second DPFR, and the one or more tracer molecule measurements based on the tracer molecule traveling through the chromatography machine, one or more column-specific transport model parameters for a column-specific transport model associated with the column of the chromatography machine.
Claim 15 recites wherein the column-specific transport model parameters include one or more of: column porosity and column dispersion.
Claim 16 recites estimating, by the processor, based on the column-specific transport model, the transport model associated with the first DPFR and the CSTR, the transport model associated with the second DPFR, and the one or more tracer molecule measurements based on the tracer molecule traveling through the chromatography machine, one or more resin transport parameters for a resin transport model associated with resin particles of the chromatography machine.
Claim 17 recites wherein the resin transport parameters include one or more of: film transport coefficient for each component and pore porosity.
Claim 18 recites wherein estimating one or more adsorption model parameters for an adsorption model associated with the experimental sample is further based on one or more of a column-specific transport model or a resin transport model.
Claim 19 recites wherein the tracer molecule is dextran.
Claim 20 recites wherein the tracer molecule is NaCl.
Claim 21 recites wherein the tracer molecule is a DNA molecule.
Claim 22 recites wherein the tracer molecule is a nanoparticle.
The limitation of claim 3 merely specifies the particular numerical inputs used in the mathematical model, which narrows the abstract idea of claim 1. The limitations of claims 4 and 5 specify that the simulated output takes the form of a chromatogram, which merely narrows the abstract ideas of claim 1. The limitations of claims 6 and 8 of identifying the experimental sample involve evaluating the fitted mathematical model to classify or label the sample, which constitute abstract ideas within the mathematical concepts and mental processes groupings. The limitations of claim 7 recite a two-stage estimation of adsorption parameters, which involves sequential mathematical optimization, constituting an abstract idea. The limitation of claim 9 involves executing the same mathematical model on two parallel or sequential model sub-systems, which constitutes an abstract idea within the mathematical concepts grouping.
The limitations of claim 10 recite repeating the adsorption-parameter estimation for a second experimental sample, which involves re-using already fitted mathematical transport parameters to fit a second set of isotherm parameters, constituting an abstract idea within the mathematical concepts grouping. The abstract idea of claim 10 is narrowed by claim 11, which specifies that the first sample is distinct from the second sample. The limitation of claim 12 lists specific mathematical variables being calculated or fitted, which merely narrows the abstract ideas of claim 1. The limitation of claim 13 lists specific mathematical variables of the isotherm model, which merely narrows the abstract ideas of claim 2. The limitations of claims 14 and 16 involve estimating additional mathematical parameters within the model, which constitute abstract ideas within the mathematical concepts grouping. The abstract ideas of claims 14 and 16 are narrowed by claims 15 and 17, which list the specific parameters to be estimated.
The limitation of claim 18 involves coupling of mathematical sub-models, which constitutes an abstract idea within the mathematical concepts grouping. The limitations of claim 19-22 specify the chemical identity of a species being modeled inside the mathematical simulation, which merely narrows the abstract ideas of claim 1. Claims 23-24 do not recite or narrow any judicial exceptions, but inherit the abstract ideas of claim 1. Therefore, claims 1-24 recite abstract ideas – namely mathematical concepts and mental processes [Step 2A, Prong One: Yes].
Prong Two
Claims 1-24 as a whole do not integrate the recited judicial exception into a practical application. A claim that recites a judicial exception [Prong One] is deemed to be directed to a judicial exception [Step 2A] unless the claim as a whole contains additional elements that integrate the exception into a practical application [Prong Two]. A claim that integrates a judicial exception into a practical application will apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, beyond generally linking the use of the judicial exception to a particular technological environment, such that the claim as a whole is more than a drafting effort designed to monopolize the exception. See MPEP §§ 2106.04(d) and 2106.05(e). A claim does not integrate a judicial exception into a practical application by reciting insignificant extra-solution activity, generally linking the exception to a particular technological environment or field of use, merely reciting to apply the exception, merely including instructions to implement an abstract idea on a computer, or merely using a computer as a tool to perform an abstract idea. See MPEP § 2106.04(d)(I). Insignificant extra-solution activities are nominal or tangential additions to a claim that are incidental to the primary process or product, including both pre-solution and post-solution activity (e.g. pre-solution data gathering for use in a process). If integrated into a practical application, the claim is eligible; otherwise, it is directed to the judicial exception, necessitating further analysis at Step 2B.
Claims 1-22 do not recite any additional elements. Claim 23 recites a computer system including a processor and one or more memories storing instructions that, when executed by the processor, cause the computer system to perform the steps of the method of claim 1. Claim 24 recites a non-transitory computer-readable storage medium storing instructions that, when executed by a processor, cause the processor to perform the steps of the method of claim 1.
The additional elements of claims 23-24 describe generic computer components that amount to nothing more than mere instructions to apply the judicial exceptions, which do not integrate into a practical application. See MPEP §§ 2106.05(b) & (f). The claims as a whole merely recite abstract ideas implemented on generic computer components without meaningful limitations that tie it to a specific technological improvement. Therefore, claims 1-24 do not contain additional elements that integrate the recited abstract ideas into a practical application [Step 2A, Prong Two: No].
Step 2B
Claims 1-24 do not include additional elements, whether considered individually or in combination, that are sufficient to amount to significantly more than the judicial exception itself. Under Step 2B, the claim is analyzed to determine whether there are any additional elements that, individually or in combination, constitute an “inventive concept" sufficient to ensure that the claim, as a whole, amounts to significantly more than the judicial exception itself. See MPEP § 2106.05; and Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 217-18, 110 USPQ2d 1976, 1981 (2014).
Claim 23 recites a computer system including a processor and one or more memories storing instructions that, when executed by the processor, cause the computer system to perform the steps of the method of claim 1. Claim 24 recites a non-transitory computer-readable storage medium storing instructions that, when executed by a processor, cause the processor to perform the steps of the method of claim 1. The additional elements of claims 23-24 are generic and conventional computer components that amount to nothing more than mere instructions to apply the judicial exceptions, which does not constitute an inventive concept sufficient to amount to significantly more than the judicial exception itself. See MPEP §§ 2106.05(b) & (f); Alice Corp. Pty. Ltd. v. CLS Bank Int'l, 573 U.S. 208, 225, 110 USPQ2d 1976, 1984 (2014); and Charles A. Lucy, Free Simulators for Virtual Chromatography Laboratory Experiments, 38(8) LCGC North America para.1 (1 August 2020).
Overall, claims 1-24 amount to no more than implementing the abstract ideas on conventional computers in a routine way. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception itself because the claims recite additional elements that equate to mere instructions to apply the recited abstract ideas in a generic way or in a generic computing environment. Therefore, claims 1-24 are rejected for failing to set forth patent eligible subject matter under 35 U.S.C. 101 because the claimed invention recites abstract ideas [Step 2A, Prong One: Yes] and the additional elements do not integrate the judicial exception into a practical application [Step 2A, Prong Two: No] and do not amount to claiming significantly more than the recited exception [Step 2B: No].
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-18 and 23-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Vijesh Kumar et al., Mechanistic modeling of ion-exchange process chromatography of charge variants of monoclonal antibody products, 1426 J. Chromatogr. A. 140-153 (24 December 2015) (hereinafter “Kumar”), as evidenced by CADET, CADET-Core, https://cadet.github.io/v5.1.X/index.html#cadet-platform (last visited 14 August 2026) (hereinafter “CADET”).
Regarding claim 1, Kumar discloses a chromatography system with a dispersed plug flow reactor (DPFR) and continuous stirred tank reactor (CSTR) before a column and another DPFR after the column. At 141 col.2 para.3; 145 col.1 para.3; Fig.1 (for a chromatography machine including a first dispersed plug flow reactor (DPFR) and a continuous stirred tank reactor (CSTR) prior to a column, and a second DPFR after the column). Kumar discloses that the initial guess values were determined from the approximate volumes and tubing length. At 145 col.2 para.3 (obtaining … geometric measurements associated with the second DPFR). Kumar teaches using MATLAB to generate system parameters based on the initial guess values. At 145 col.2 para.3 (generating, by a processor, transport model parameters for a transport model associated with the second DPFR based on the geometric measurements). Kumar discloses injecting a suitable tracer into the chromatography system to capture measurements based on the sample flow through the system. At 145 col.2 para.4 (feeding a tracer molecule into the chromatography machine; capturing one or more tracer molecule measurements based on the tracer molecule traveling through the chromatography machine). Kumar teaches estimating the system parameters for the DPFR and CSTR before the column based on the parameters of the DPFR after the column and the flow rates determined from the suitable tracer. At 145 col.1 paras.2-4; col.2 para.4 (estimating, by the processor, based on the transport model associated with the second DPFR and the one or more tracer molecule measurements based on the tracer molecule traveling through the chromatography machine, one or more transport model parameters for a transport model associated with the first DPFR and the CSTR).
Regarding claim 2, Kumar discloses feeding a monoclonal antibody (mAb) sample into the chromatography system to capture values based on the sample traveling through the system. At 144 col.1 para.8 (the method of claim 1, further comprising: feeding an experimental sample into the chromatography machine; capturing one or more experimental measurements based on the experimental sample traveling through the chromatography machine). Kumar then performs inverse fitting to estimate the adsorption model parameters based on the transport parameters and measured experimental values. At 146 col.1 para.1 – col.2 para.1; 147 col.1 para.2 – col.2 para.3 (estimating, by the processor, based on the one or more experimental measurements based on the experimental sample traveling through the chromatography machine, the estimated one or more transport model parameters for the transport model associated with the first DPFR and the CSTR, and the transport parameters for the transport model associated with the second DPFR, one or more adsorption model parameters for an adsorption model associated with the experimental sample).
Regarding claim 3, Kumar discloses that the initial guess values were determined from the approximate volumes and tubing length. At 145 col.2 para.3 (wherein the geometric measurements include tubing diameter measurements and tubing length measurements associated with the second DPFR).
Regarding claims 4 and 5, Kumar discloses that measurements are captured based on a chromatogram. At 145 col.1 para.5 (claim 4: wherein the one or more tracer molecule measurements are captured based on a chromatogram associated with the tracer molecule traveling through the chromatography machine; claim 5: wherein the one or more experimental measurements are captured based on a chromatogram associated with the experimental sample traveling through the chromatography machine).
Regarding claims 6 and 8, Kumar discloses separating and marking charge variants of mAb. At Fig.3 caption (identifying, by the processor, the experimental sample based on the adsorption model associated with the experimental sample).
Regarding claim 7, Kumar discloses estimating the adsorption model parameters using an inverse method before performing a step elution and gradient elution to obtain a second estimated adsorption parameters. At 147 col.2 para.3 – 148 col.1 para.2 (wherein the estimating the one or more adsorption model parameters for the adsorption model associated with the experimental sample is a first estimating of a first one or more adsorption parameters for a first adsorption model associated with the experimental sample, and further comprising: a second estimating, by the processor, of a second one or more adsorption parameters for a second adsorption model associated with the experimental sample based on a range associated with the first one or more binding parameters for the first adsorption model associated with the experimental sample).
Regarding claim 9, Kumar discloses using a series of DPFRs and CSTRs. At 141 col.1 para.3; Fig.1 (wherein the first DPFR and a CSTR prior to the column, and the second DPFR after the column are part of an inlet flow path of the chromatography machine, and wherein the chromatography machine further includes a sample flow path having a first DPFR and a CSTR prior to a sample flow path column, and a second DPFR after the sample flow path column, and wherein the steps of claim 1 are further performed for the first DPFR and the CSTR prior to the sample flow path column, and the second DPFR after the sample flow path column).
Regarding claims 10 and 11, Kumar examines multiple charge variants of the same mAb product under the same system model such that transport parameters are held while binding parameters are fitted for the difference species. At 144 col.2 paras.4-5 (claim 10: wherein the experimental sample is a first experimental sample, and further comprising: feeding a second experimental sample into the chromatography machine; capturing one or more second experimental measurements based on the second experimental sample traveling through the chromatography machine; and estimating, by the processor, based on the one or more second experimental measurements based on the second experimental sample traveling through the chromatography machine, the estimated one or more transport model parameters for the transport model associated with the first DPFR and the CSTR, and the transport parameters for the transport model associated with the second DPFR, one or more adsorption model parameters for an adsorption model associated with the second experimental sample; claim 11: wherein the second experimental sample is distinct from the first experimental sample).
Regarding claim 12, Kumar discloses that the transport model parameters include dispersion coefficient in DPFR. At 145 col.1 para.3 (wherein the transport model parameters include one or more of: dispersion coefficient in DPFR, volume of DPFR, cross-section area of DPFR, and volume of CSTR).
Regarding claim 13, Kumar discloses fitting an extended Langmuir isotherm, which relies on adsorption and desorption coefficients. At 142 col.2 para.7 (wherein the adsorption model parameters include one or more of: adsorption coefficient, desorption coefficient, characteristic charge, and shielding factor).
Regarding claims 14-15, Kumar discloses using the transport parameters and measured values to calculate the column porosities and dispersion using the inverse method. At 145 col.1 para.6 (claim 14: further comprising estimating, by the processor, based on the transport model associated with the first DPFR and the CSTR, the transport model associated with the second DPFR, and the one or more tracer molecule measurements based on the tracer molecule traveling through the chromatography machine, one or more column-specific transport model parameters for a column-specific transport model associated with the column of the chromatography machine; claim 15: wherein the column-specific transport model parameters include one or more of: column porosity and column dispersion).
Regarding claims 16-17, Kumar discloses using the inverse method to estimate the pore diffusion coefficient and the film diffusion coefficient. At 146 col.2 para.3 – 147 col.1 para.1 (claim 16: further comprising estimating, by the processor, based on the column-specific transport model, the transport model associated with the first DPFR and the CSTR, the transport model associated with the second DPFR, and the one or more tracer molecule measurements based on the tracer molecule traveling through the chromatography machine, one or more resin transport parameters for a resin transport model associated with resin particles of the chromatography machine; claim 17: wherein the resin transport parameters include one or more of: film transport coefficient for each component and pore porosity).
Regarding claim 18, Kumar discloses that adsorption parameters are estimated based on the column parameters simultaneously with the pore diffusion coefficient and the film diffusion coefficient. At 146 col.2 paras.2-3 (wherein estimating one or more adsorption model parameters for an adsorption model associated with the experimental sample is further based on one or more of a column-specific transport model or a resin transport model).
Regarding claims 23 and 24, Kumar discloses that all modeling and inverse fitting is performed using the CADET framework. At 144 col.1 para.4. CADET is an open-source program that can be downloaded for execution by a processor. See CADET at §§ CADET Platform – Installation (claim 23: a computer system including a processor and one or more memories storing instructions that, when executed by the processor, cause the computer system to perform the steps of the method of claim 1; claim 24: a non-transitory computer-readable storage medium storing instructions that, when executed by a processor, cause the processor to perform the steps of the method of claim 1).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim 19 is rejected under 35 U.S.C. 103 as being unpatentable over Kumar in view of Thermo Fisher Scientific, Fluorescent and Biotinylated Dextrans—Section 14.5 (16 August 2015) (hereinafter “Thermo Fisher”).
Regarding claim 19, Kumar teaches the method of claim 1 (see 102 rejection above). Kumar does not explicitly teach the tracer molecule being dextran. However, Thermo Fisher discloses that dextrans are widely used as tracers for various applications. A person having ordinary skill in the art could apply dextran as the tracer molecule used in the method of Kumar. One of ordinary skill in the art would reasonably predict that the substitution would work because Kumar teaches using any suitable tracer molecule, and Thermo Fisher teaches that dextran is a widely used tracer. Simple substitution of one known element for another to obtain predictable results is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007); and MPEP § 2143, B.
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Kumar in view of Cytiva, Column efficiency testing, GE Healthcare Application note 28-9372-07 AA (May 2020) (hereinafter “Cytiva”).
Regarding claim 20, Kumar teaches the method of claim 1 (see 102 rejection above). Kumar does not explicitly teach the tracer molecule being NaCl. However, Cytiva discloses using NaCl as a tracer molecule for chromatography applications. At 2 col.2 para.5. Cytiva notes that a minimum of 0.4 M NaCl in the eluent has to be used to suppress charge interaction effects between the tracer and the chromatography medium to avoid misleading test results. Id. A person having ordinary skill in the art could apply NaCl as the tracer molecule used in the method of Kumar. One of ordinary skill in the art would reasonably predict that the substitution would work because Kumar teaches using any suitable tracer molecule, and Cytiva teaches that NaCl is an acceptable tracer for chromatography when a minimum of 0.4 M NaCl is used. Simple substitution of one known element for another to obtain predictable results is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007); and MPEP § 2143, B.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Kumar in view of Gediminas Mikutis et al., Silica-Encapsulated DNA-Based Tracers for Aquifer Characterization, 52(21) Environ. Sci. Technol. 12142–12152 (2 October 2018) (hereinafter “Mikutis”).
Regarding claim 21, Kumar teaches the method of claim 1 (see 102 rejection above). Kumar does not explicitly teach the tracer molecule being DNA. However, Mikutis discloses using DNA as a tracer molecule, and notes that DNA-based tracers are applicable to chromatography applications. At 12148 col.1 para.3. A person having ordinary skill in the art could apply DNA as the tracer molecule used in the method of Kumar. One of ordinary skill in the art would reasonably predict that the substitution would work because Kumar teaches using any suitable tracer molecule, and Mikutis teaches that NaCl is an acceptable tracer for chromatography applications. Simple substitution of one known element for another to obtain predictable results is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007); and MPEP § 2143, B.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Kumar in view of Guor-Tzo Wei et al., Shape Separation of Nanometer Gold Particles by Size-Exclusion Chromatography, 71(11) Anal. Chem. 2085-91 (1 June 1999) (hereinafter “Wei”).
Regarding claim 22, Kumar teaches the method of claim 1 (see 102 rejection above). Kumar does not explicitly teach the tracer molecule being a nanoparticle. However, Wei discloses using gold nanoparticles as tracer molecules for chromatography applications. At 2085 col.1 para.1. A person having ordinary skill in the art could apply nanoparticles as the tracer molecule used in the method of Kumar. One of ordinary skill in the art would reasonably predict that the substitution would work because Kumar teaches using any suitable tracer molecule, and Wei teaches that a nanoparticle is an acceptable tracer for chromatography applications. Simple substitution of one known element for another to obtain predictable results is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007); and MPEP § 2143, B.
Conclusion
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/E.A.D./ Examiner, Art Unit 1686
/LARRY D RIGGS II/ Supervisory Patent Examiner, Art Unit 1686
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