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 .
Election/Restrictions
Applicant's election with traverse of using a gradient boosting model and specific performance factors in the reply filed on 18 May 2026 is acknowledged. The traversal is on the ground(s) that Groups I-III do not simply require a machine learning model for predicting values related to chromatographic purification This is not found persuasive because the independent claim recites processors receiving descriptors regarding a protein, predicting performance based on a machine learning model, and outputting a result based on the calculation. Shaver (WO 2019/165148 A1; previously cited on the 21 October 2022 IDS form) teaches predicting yield and purity – interpreted as performance factors – based on chromatographic data and outputting the conditions (Fig. 1; abstract), utilizing machine learning to (pg. 3-4, paragraph [16]) optimize the process. Therefore, Shaver is considered to teach the shared technical features. The requirement is still deemed proper and is therefore made FINAL.
Status of the Claims
Claims 1-20 are pending.
Claims 8-9 and 14-15 are withdrawn following the election filed 18 May 2026, with claims 10-13 being elected.
Claims 1-7, 10-13, and 16-19 are examined herein.
Priority
As detailed on the 31 January 2023 filing receipt, the application claims priority as early as 23 April 2020 to provisional application 63/014,273. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Information Disclosure Statement
Information disclosure statements (IDS) were filed on 21 October 2022 and 04 March 2024. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the references are being considered by the examiner.
Claim Objections
Claims 1-2, 13, and 19 are objected to because of the following informalities: elements (i) and (ii) should not be separated by a comma. For instance, in claim 1: “one or both of (i) the predicted performance indicator[[,]] and (ii) an indication...”
Appropriate correction is required.
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 1-7, 10-13, and 16-19 are rejected under 35 USC § 101 because the claimed inventions are directed to an abstract idea without significantly more. "Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection" (MPEP 2106.04 § I). Abstract ideas include mathematical concepts, and procedures for evaluating, analyzing or organizing information, which are a type of mental process (MPEP 2106.04(a)(2)). The claims as a whole, considering all claim elements individually and in combination, are directed to a judicial exception at Step 2A, Prong 2, and the additional elements of the claims, considered individually and in combination, do not provide significantly more at Step 2B than the abstract idea of selecting chromatographic parameters.
MPEP 2106 organizes JE analysis into Steps 1, 2A (Prong One & Prong Two), and 2B as analyzed below.
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter (MPEP 2106.03)?
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of
nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Step 1: Are the claims directed to a 101 process, machine, manufacture, or composition of matter (MPEP 2106.03)?
The claims are directed to methods (claims 1-7, 10-13, and 16-17), a computer system (claim 19), and a non-transitory computer-readable medium (claim 18), each of which falls within one of the categories of statutory subject matter. [Step 1: Yes]
Step 2A, Prong One: Do the claims recite a judicially recognized exception, i.e., a law of nature, a natural phenomenon, or an abstract idea (MPEP 2106.04(a-c))?
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. MPEP § 2106.04(a)(2) further explains that abstract ideas are defined as:
• mathematical concepts (mathematical formulas or equations, mathematical relationships
and mathematical calculations) (MPEP 2106.04(a)(2)(I));
• certain methods of organizing human activity (fundamental economic principles or practices, managing personal behavior or relationships or interactions between people) (MPEP 2106.04(a)(2)(II)); and/or
• mental processes (concepts practically performed in the human mind, including observations, evaluations, judgments, and opinions) (MPEP 2106.04(a)(2)(III)).
Mathematical concepts recited in the claims include: predicting a performance indicator based on process parameters and molecular descriptors using a machine learning model including a gradient boosting algorithm (claims 1 and 18-19), where gradient boosting is considered a mathematical concept; predicting a process parameter based on performance indicators and molecular descriptors using a machine learning model including a gradient boosting algorithm (claim 2), where gradient boosting is considered a mathematical concept; descriptions of the parameters for the models (claims 3-4, 6-7, and 10-12); determining a descriptor based on an experimental measurement (claim 5), where the measuring is not required as an active step and descriptors are exemplified in the disclosure as mathematical representations (pg. 2, paragraph [7]); and predicting a yield based on the parameters (claim 13).
Mental processes, defined as concepts practically performed in the human mind such as steps of observing, evaluating, or judging information, recited in claims include selecting parameter values (claim 17).
Thus, the claims do not recite elements in addition to the abstract ideas which integrate the judicial exception into a practical application and so the claims are interpreted as directed to one or more judicial exceptions. [Step 2A Prong One: Yes]
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application by an additional element (MPEP 2106.04(d))?
Because the claims recite judicial exceptions, direction under Step 2A Prong Two provides that the claims must be examined further to determine whether they integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d)(I); MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d)(III)).
Elements in addition to the abstract ideas recited in the claims are: a computing system with processors (claims 1-2), outputting using a user interface (claims 1-2, 13, and 18-20), performing the chromatographic process (claims 16-17), one or more non-transitory, computer-readable media storing instructions executed by one or more processors of a computing system (claim 18), and a computing system comprising processors and one or more non-transitory, computer-readable media (claim 19).
The claims comprising computer components do not describe any specific computational steps by which the computer performs or carries out the abstract idea, nor do they provide any details of how specific structures of the computer are used to implement these functions. The claims state nothing more than that a generic computer performs the functions that constitute the abstract idea. Hence, these are mere instructions to apply the abstract idea using a computer, and therefore the claim does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
The claim elements recite receiving data and outputting data via a user interface. Receiving data to perform the predicting step is considered to be a necessary data gathering step to perform the abstract predicting step, while presenting the output is considered be necessary data outputting. These steps are insignificant extra-solution activity preceding and following the abstract steps of the claims which do not integrate the abstract ideas into a practical application (MPEP 2106.05(g)).
The claim elements reciting performing the chromatographic process are interpreted as mere instructions to apply the abstract idea (MPEP 2106.05(f)).
[Step 2A Prong Two: No]
Step 2B: Do the claims recite a non-conventional arrangement of elements in addition to any identified judicial exception(s) (MPEP 2106.05)?
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself. Step 2B of 101 analysis determines whether the claims contain additional elements that amount to an inventive concept, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
Elements in addition to the abstract ideas recited in the claims are: a computing system with processors (claims 1-2), outputting using a user interface (claims 1-2, 13, and 18-20), performing the chromatographic process (claims 16-17), one or more non-transitory, computer-readable media storing instructions executed by one or more processors of a computing system (claim 18), and a computing system comprising processors and one or more non-transitory, computer-readable media (claim 19).
The claims recite a computer, interpreted as instructions to apply the abstract idea using a computer, where the computer does not impose meaningful limitations on the judicial exceptions, which can be performed without the use of a computer (MPEP 2106.04(d) § I; and MPEP 2106.05(f)). Storing data on a computer, as in memory, is a conventional computer function (Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015); OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93; MPEP 2106.05(d)).
The courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a merely generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93 (storing and retrieving information in memory), as discussed in MPEP 2106.05(d)(II)(i)).
Bensch (Chemical Engineering and Technology 28(11): 1274-1284, 2005; newly cited) teaches, in a review of optimizing parameters for chromatographic screening, performing downstream chromatography following screening steps (pg. 1283, Section 5).
Therefore, the recited additional elements, alone or in combination with the judicial exceptions, do not appear to provide an inventive concept. [Step 2B: No]
Conclusion: Claims are Directed to Non-statutory Subject Matter
For these reasons, the claims, when the limitations are considered individually and as a whole,
are directed to an abstract idea and lack an inventive concept. Hence, the claimed invention does not
constitute significantly more than the abstract idea, so the claims are rejected under 35 USC § 101 as
being directed to non-statutory subject matter.
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.
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 nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-7, 10-11, 13, and 18-19
Claims 1, 3-7, 10-11, 13, and 18-19 are rejected under 35 U.S.C. 103 as being unpatentable over Shaver (WO 2019/165148 A1; previously cited on the 21 October 2022 IDS form) in view of Jungbauer (WO 2017/174580 A1; previously cited on the 04 March 2024 IDS form).
Claim 1 recites receiving, by one or more processors of a computing system, one or more process
parameter values associated with a hypothetical chromatography process.
Shaver teaches determining optimal chromatographic processing for therapeutics (pg. 1, paragraph [2]) and inputting purification conditions such as pH levels (Fig. 3, Ref 310), where process parameters are interpreted as conditions of the chromatographic purification.
Claim 1 recites receiving, by the one or more processors, one or more molecular descriptors descriptive of the therapeutic protein.
Shaver teaches using structure data, where structure data is interpreted as read on by molecular descriptors, where data includes information about hydrophobicity, polarity, and charges (pg. 6, paragraph [22]).
Claim 1 recites predicting, by the one or more processors, a performance indicator for the hypothetical chromatography process at least by analyzing the one or more process parameters and the one or more molecular descriptors using a machine learning model, wherein the machine learning model is a model selected from a group consisting of (i) a regression tree model, (ii) an extreme gradient boost model, and (iii) an elastic net model.
Shaver teaches predicting measures of performance for various chromatographic techniques (pg. 5, paragraph [20]) and outputting purification conditions (Fig. 1, Ref. 140). Shaver teaches utilizing machine learning to optimize the purification process (pg. 3-4, paragraph [16]) but not, for instance, gradient boosting.
Claim 1 recites causing, by the one or more processors, one or both of (i) the predicted performance indicator and (ii) an indication of whether the predicted performance indicator satisfies one or more acceptability criteria, to be presented to a user via a user interface.
Shaver teaches determining optimal yield (pg. 5, paragraph [17]), where yield is a performance indicator and an output device such as a display (pg. 23, paragraph [58]).
Jungbauer teaches boosting (paragraph [236]).
Claim 18 recites one or more non-transitory, computer-readable media storing instructions that, when executed by one or more processors of a computing system, cause the computing system to perform the method of claim 1.
The claim limitations are taught by the above combination of Shaver and Jungbauer. Additionally, Shaver teaches “non-transient memory technologies” (pg. 22, paragraph [60]).
Claim 19 recites a computing system comprising one or more processors and one or more non-transitory, computer-readable media storing instructions that, when executed by the one or more processors, cause the computing system to perform the method of claim 1.
The claim limitations are taught by the above combination of Shaver and Jungbauer. Additionally, Shaver teaches a system including processors and memory that can store programs (pg. 21, paragraph [55]).
Claim 3 recites the hypothetical chromatography process is a process selected from a group consisting of a hypothetical cation-exchange chromatography (CEX) process; a hypothetical size-exclusion chromatography (SEC) process; and a Protein A chromatography process.
Shaver teaches selecting chromatographic techniques, including ion exchange chromatography and size exclusion chromatography (pg. 6, paragraph [23]).
Claim 4 recites determining, by the one or more processors, at least one of the one or more molecular descriptors based on sequence information associated with the therapeutic protein.
Shaver teaches measuring performance based on sequence data variables (pg. 8, paragraph [27]).
Claim 5 recites determining, by the one or more processors, at least one of the one or more molecular descriptors based on an experimental measurement of a physical characteristic of the therapeutic protein.
Shaver teaches measuring performance of a protein (pg. 27, paragraphs [71-72]).
Claim 6 recites at least one of the one or more molecular descriptors is a function of pH level.
Shaver teaches molecules can be separated based on charge (pg. 2, paragraph [13]), where charge is affected by pH level.
Claim 7 recites the one or more process parameter values include one or more of:
buffer pH; elution buffer pH; elution buffer conductivity; elution buffer molarity; gradient slope; linear velocity; load conductivity; load factor; load pH; or stop collect.
Shaver teaches pH level as a purification condition the model uses to determine optimal conditions (pg. 7, paragraph [26]).
Claim 10 recites the machine learning model is the extreme gradient boost model.
Jungbauer teaches boosting (paragraph [236]).
Claim 11 recites the performance indicator includes: CEX % Acidic; CEX % Main; step yield; rCE-SDS % Main; rCE-SDS % LMW; cIEF % Acidic; cIEF % Basic; or cIEF % Main.
Shaver teaches the yield of several steps (pg. 4, paragraph [17]).
Claim 13 recites predicting, by the one or more processors, a yield for the hypothetical chromatography process at least by analyzing process parameters and molecular descriptors using an additional machine learning model, wherein the additional machine learning model is another extreme
gradient boost model.
Shaver teaches yield prediction (abstract) and one or more models for analyzing protein data (pg. 20, paragraph [54]) and Jungbauer teaches boosting for variable selection (pg. 54, paragraph [236]).
Claim 13 recites causing, by the one or more processors, one or both of (i) the predicted yield and (ii) an indication of whether the predicted yield satisfies one or more additional acceptability criteria, to be presented to the user via the user interface.
Shaver teaches an output device such as a display (pg. 22, paragraph [59]).
Combining Shaver and Jungbauer
An invention would have been obvious to one of ordinary skill in the art if some motivation in the prior art would have led that person to modify prior art reference teachings to arrive at the claimed invention prior to the effective filing date of the invention. One would have been motivated to combine the work of Jungbauer with that of Shaver because Shaver teaches machine learning methods but not boosting methods, which are taught by Jungbauer, where an advantage of such a method, as taught by Jungbauer, is that boosting as a variable selection tool constructs the final model in a stepwise process by minimizing a loss-function and preserving the additivity of the model structure and provides a variable importance measure via predictor selection frequencies and therefore a desirable method for variable selection (paragraph [236]). Both Shaver and Jungbauer are directed to the shared field of endeavor of chromatographic purification control and prediction and their combination is prima facie obvious.
Claim 12
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Shaver in view of Jungbauer as applied to claims 1, 3-7, 10-11, 13, and 18-19 above and further in view of Chen (Journal of Chromatography B 877: 3012-3018, 2009; newly cited).
Claim 12 recites the performance indicator includes SEC% HMW.
Shaver and Jungbauer do not teach the percent high molecular weight in size exclusion chromatography.
Chen teaches SEC %HMW as a relevant parameter in size exclusion chromatography (Fig. 6 caption).
Combining Shaver, Jungbauer, and Chen
The previously combined works of Shaver and Jungbauer teach optimization for performance indicators such as yield and size exclusion chromatography, but not percent high molecular weight in size exclusion chromatography. Chen teaches SEC %MHW as a relevant variable in screening proteins using size exclusion chromatography (Fig. 6 caption). Therefore, one of ordinary skill in the art could have substituted an indicator such as yield with %HMW with predictable results. MPEP 2143B pertains.
Claim 16
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Shaver in view of Jungbauer as applied to claims 1, 3-7, 10-11, 13, and 18-19 above and further in view of Peris-Vicente (Chapter 14, 52 pgs; in Analytical Separation Science 1st ed, 2015; newly cited).
Claim 16 recites selecting one or more process parameter values for a chromatography process for the therapeutic protein based on the presented performance indicator and/or the presented indication and performing the chromatography process for the therapeutic protein according to the selected process parameter values.
Shaver teaches selecting options (pg. 37, paragraphs [114-115]).
Peris-Vicente teaches validating optimized parameters experimentally (pg. 2, third paragraph), where experimental validation is interpreted as performing chromatography.
Combining Shaver, Jungbauer, and Peris-Vicente
An invention would have been obvious to one of ordinary skill in the art if some motivation in the prior art would have led that person to modify prior art reference teachings to arrive at the claimed invention prior to the effective filing date of the invention. One would have been motivated to combine the work of Peris-Vicente with the previously combined works because Peris-Vicente teaches validating the determined parameters experimentally, which would be the natural extension of determining such values as whether the method will function in the proper way (pg. 1, second paragraph) when the bioinformatically determined variables are tested experimentally (pg. 2, third paragraph). Further, Shaver teaches at least using determined conditions to purify proteins and thus an overall goal in this field of endeavor (pg. 2, paragraph [12]). The combined art is directed to parameterization and optimization in chromatography and their combination is prima facie obvious.
Claim 2
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Shaver in view of Jungbauer and Golshan-Shirazi (Journal of Chromatography 536: 57-73, 1991; newly cited).
Claim 2 recites the limitations of claim 1 except performance indicators are used to determine process parameters.
The limitations are taught by Shaver and Jungbauer above, with Golshan-Shirazi teaching optimizing column characteristics for a required yield (pg. 64, first paragraph), where the required yield is considered to be a performance indicator and the column characteristics are process parameters.
Combining Shaver, Jungbauer, and Golshan-Shirazi
An invention would have been obvious to one of ordinary skill in the art if some motivation in the prior art would have led that person to modify prior art reference teachings to arrive at the claimed invention prior to the effective filing date of the invention. One would have been motivated to combine the work of Golshan-Shirazi with Shaver and Jungbauer because Golshan-Shirazi teaches a required purity and yield (e.g., end of pg. 63, beginning of pg. 64), where a required yield necessitates optimization of column variables. Given the two types of variables – performance variables and process variables – are used in a similar way as Shaver and Jungbauer, depending on whether one desires optimization of process variables or performance variables. The combined art is directed to the shared field of optimizing chromatography conditions and their combination is prima facie obvious.
Claim 17
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Shaver in view of Jungbauer and Golshan-Shirazi as applied to claim 2 above and further in view of Peris-Vicente.
Claim 17 recites selecting one or more process parameter values for a chromatography process for the therapeutic protein based on the presented predicted process parameter value, and/or the
predicted accuracy range and performing the chromatography process for the therapeutic protein according to the selected process parameter values.
Shaver teaches selecting options (pg. 37, paragraphs [114-115])).
Peris-Vicente teaches validating optimized parameters experimentally (pg. 2, third paragraph), where experimental validation is interpreted as performing chromatography.
Combining Shaver, Jungbauer, Golshan-Shirazi, and Peris-Vicente
An invention would have been obvious to one of ordinary skill in the art if some motivation in the prior art would have led that person to modify prior art reference teachings to arrive at the claimed invention prior to the effective filing date of the invention. One would have been motivated to combine the work of Peris-Vicente with the previously combined works because Peris-Vicente teaches validating the determined parameters experimentally, which would be the natural extension of determining such values as whether the method will function in the proper way (pg. 1, second paragraph) when the bioinformatically determined variables are tested experimentally (pg. 2, third paragraph). Further, Shaver teaches at least using determined conditions to purify proteins and thus an overall goal in this field of endeavor (pg. 2, paragraph [12]). The combined art is directed to parameterization and optimization in chromatography and their combination is prima facie obvious.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Robert J Kallal whose telephone number is (571)272-6252. The examiner can normally be reached Monday through Friday 8 AM - 4 PM EST.
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/Robert J. Kallal/Examiner, Art Unit 1685
Prosecution Insights