DETAILED ACTION
The Applicant’s response, received 07 November 2025, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 .
Status of the Claims
Claims 1-20 are pending.
Claims 1-20 are rejected.
Priority
The effective filing date of the claimed invention is 06 June 2024.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 18 September 2025 and 10 November 2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Claim Interpretation
Claims 3, 4, 8-12, and 16-19 recite the limitation “structure token(s).” This limitation is interpreted to mean a unit that is representative of a sequence of data (e.g., text, or amino acids) that has been converted into smaller parts (i.e., tokens) in order to efficiently encode more complex structures (e.g., sentences, or proteins) for analyses using natural language processing (NLP) and machine learning algorithms (Specification, ¶¶ [0050] & [0068]).
Claims 1, 9, 13, 17, and 20 recite the limitation “prediction quality evaluation.” This limitation is interpreted to mean a function and/or approach for evaluating a predicted sequence and using an evaluation score to determine which candidates produce improved results (Specification, ¶¶ [0040], [0216], [0223], & [0245]).
Claims 1-3, 13, 14, and 20 recite the limitation “property” and/or “properties.” This limitation is interpreted to mean a protein-related characteristic or desired property of a protein, such as its sequence, structure, secondary structure, solvent accessible surface area, and function (Specification, ¶¶ [0042] & [0077]).
Claims 1, 12, 13, 19, and 20 recite the limitation “predict” and/or “predicting.” The broadest reasonable interpretation of this limitation comprises a mathematical function that gives the probabilities of occurrence of possible outcomes (Specification, ¶¶ [0001], [0038], [0221], [0233], & [0234]).
Claim Rejections - 35 USC § 112
The rejection of claims 1-20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, in the Office action mailed 21 July 2025 is withdrawn in part in view of the amendment received 07 November 2025, as noted below.
The Applicant’s amendment received 07 November 2025 has been fully considered, however after further consideration new grounds of rejection are raised in view of the amendment.
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 1-20 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.
New grounds of rejection:
Claim 1 is indefinite for reciting “discovering and unmasking one or more other properties…” because it is not clear as to whether the “discovering” happens before the “unmasking.” This limitation is interpreted as “unmasking and discovering one or more other properties….”
Claims 2-12 are indefinite for depending from independent claim 1 and for failing to remedy the indefiniteness of claim 1.
Claim 13 is indefinite for reciting “discover and unmask one or more other properties…” because it is not clear as to whether the limitation “discover” happens before the limitation “unmask.” This limitation is interpreted as “unmask and discover one or more other properties….”
Claims 14-19 are indefinite for depending from independent claim 13 and for failing to remedy the indefiniteness of claim 13.
Claim 20 is indefinite for reciting “discovering and unmasking one or more other properties…” because it is not clear as to whether the “discovering” happens before the “unmasking.” This limitation is interpreted as “unmasking and discovering one or more other properties….”
The following rejections in the Office action mailed 21 July 2025 are maintained:
Claim 13 is indefinite for reciting “one or more processors configured to…effect a physical synthesis of the protein” because it is not clear if the system requires a processor to be configured to control external equipment used in the synthesis process (e.g., a synthetic protein synthesizer device), or if the system requires that the one or more processors only output instructions for synthesis of a protein. Because the system does not comprise equipment for actually synthesizing a protein, this limitation is interpreted to mean that the one or more processors output/transmit instructions for the synthesis of a protein.
Claims 14-19 are indefinite for depending from independent claim 13 and for failing to remedy the indefiniteness of claim 13.
Claim 20 is indefinite for reciting “…a non-transitory computer readable storage medium and comprising computer instructions for…causing a physical synthesis of the protein” because it is not clear if the non-transitory computer readable storage medium requires the computer instructions to control external equipment used in the synthesis process (e.g., a synthetic protein synthesizer device), or if the non-transitory computer readable storage medium only stores instructions for the synthesis of a protein. Because the system claim does not comprise equipment for actually synthesizing a protein, this limitation is interpreted to mean that the non-transitory computer readable storage medium only stores instructions for the synthesis of a protein.
Claim Rejections - 35 USC § 101
The Applicant’s amendment received 07 November 2025 has been fully considered, however after further consideration, the rejection of claims 1-20 in the Office action mailed 21 July 2025 is maintained with modification in view of the amendment.
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 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea and a law of nature without significantly more. The claims recite: (a) mathematical concepts, (e.g., mathematical relationships, formulas or equations, mathematical calculations); (b) mental processes, i.e., concepts performed in the human mind, (e.g., observation, evaluation, judgement, opinion); and (c) a law of nature (e.g., naturally occurring relationships).
Subject matter eligibility evaluation in accordance with MPEP 2106.
Eligibility Step 1: Step 1 of the eligibility analysis asks: Is the claim to a process, machine, manufacture or composition of matter?
Claims 1-12 are directed to a method (i.e., a process) of predicting protein-related properties associated with amino acid positions in a protein; claims 13-19 are directed to a system comprising one or more processors (i.e., a machine or manufacture); and claim 20 is directed to a non-transitory computer readable storage medium (i.e., a machine or manufacture).
Therefore, these claims are encompassed by the categories of statutory subject matter, and thus satisfy the subject matter eligibility requirements under step 1.
[Step 1: YES]
Eligibility Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in Prong Two whether the recited judicial exception is integrated into a practical application of that exception.
Eligibility Step 2A Prong One: In determining whether a claim is directed to a judicial exception, examination is performed that analyzes whether the claim recites a judicial exception, i.e., whether a law of nature, natural phenomenon, or abstract idea is set forth or described in the claim.
Independent claim 1 recites the following steps which fall within the mental processes and/or mathematical concepts groupings of abstract ideas:
using a machine learning model to predict a plurality of candidates for a property of a selected amino acid position included in the second portion of the sequence of the protein that is masked (i.e., mental processes and mathematical concepts);
selecting property candidates from the plurality of candidates for the property (i.e., mental processes);
for each selected property candidate of the plurality of property candidates, using the selected property candidate as an input to the machine learning model to predict properties for one or more other amino acid positions of the second portion of the sequence of the protein included in a corresponding candidate set of properties (i.e., mental processes and mathematical concepts);
evaluating the corresponding candidate sets of properties for the selected property candidates using a prediction quality evaluation (i.e., mental processes);
based on the evaluation of the corresponding candidate sets of properties, choosing one of the selected property candidates as a determined result property of the selected amino acid position to unmask and discover the property of the selected amino acid position included in the second portion of the sequence (i.e., mental processes); and
discovering and unmasking one or more other properties of the second portion of the sequence that were masked using the determined result property of the selected amino acid position as an input to the machine learning model to predict a plurality of candidates for a property of a different selected amino acid position included in the second portion of the sequence of the protein (i.e., mental processes and mathematical concepts).
Independent claim 13 recites a system comprising a memory coupled to at least one of one or more processors and configured to provide instructions for executing the abstract ideas recited by independent claim 1.
Independent claim 20 recites a computer program product, the computer program product being embodied in a non-transitory computer readable storage medium and comprising computer instructions for executing the abstract ideas recited by independent claim 1.
Independent claims 1, 13, and 20, and those claims dependent therefrom, further recite a law of nature by associating genomic data (amino acid position properties) with phenotypes (protein properties, e.g., structures and/or functions), i.e., a genotype-phenotype correlation (MPEP 2106.04(b)).
Dependent claim 2 further recites:
wherein the determined result property of the selected amino acid position included in the protein corresponds to a structure property of the selected amino acid position included in the protein (i.e., mental processes).
Dependent claim 3 further recites:
wherein one of the predicted plurality of candidates for the property of the selected amino acid position is associated with a structure token (i.e., mental processes).
Dependent claim 4 further recites:
wherein the structure token references neighboring amino acids of the protein (i.e., mental processes).
Dependent claim 5 further recites:
selecting the selected amino acid position based on a search criterion (i.e., mental processes).
Dependent claim 6 further recites:
wherein the search criterion includes randomly selecting the selected amino acid position included in the protein (i.e., mental processes).
Dependent claim 7 further recites:
wherein the machine learning model is a multi-track model (i.e., mental processes and mathematical concepts).
Dependent claim 8 further recites:
decoding one or more structure tokens associated with the second portion of the sequence (i.e., mental processes).
Dependent claim 9 further recites:
wherein using the prediction quality evaluation includes analyzing the decoded one or more structure tokens (i.e., mental processes and mathematical concepts).
Dependent claim 10 further recites:
wherein the decoded one or more structure tokens include coordinates of one or more atoms of the protein (i.e., mental processes).
Dependent claim 11 further recites:
creating a structure input sequence based on at least one or more structure tokens associated with the second portion of the sequence (i.e., mental processes); and
generate a candidate protein sequence (i.e., mental processes and mathematical concepts).
Dependent claim 12 further recites:
creating a structure input sequence using at least one or more structure tokens associated with the second portion of the sequence (i.e., mental processes);
selecting a candidate structure token from the structure input sequence associated with a second amino acid position of the protein (i.e., mental processes);
predicting candidate structure token results associated with the second amino acid position of the protein (i.e., mental processes and mathematical concepts); and
comparing the predicted candidate structure token results to the candidate structure token (i.e., mental processes).
Dependent claim 14 further recites:
wherein the determined result property of the selected amino acid position included in the protein corresponds to a structure property of the selected amino acid position included in the protein (i.e., mental processes).
Dependent claim 15 further recites:
the machine learning model is a multi-track model (i.e., mental processes and mathematical concepts).
Dependent claim 16 further recites:
decode one or more structure tokens associated with the second portion of the sequence (i.e., mental processes).
Dependent claim 17 further recites:
wherein using the prediction quality evaluation function includes analyzing the decoded one or more structure tokens (i.e., mental processes and mathematical concepts).
Dependent claim 18 further recites:
create a structure input sequence based on at least one or more structure tokens associated with the second portion of the sequence (i.e., mental processes); and
generate a candidate protein sequence (i.e., mental processes).
Dependent claim 19 further recites:
create a structure input sequence using at least one or more structure tokens associated with the second portion of the sequence (i.e., mental processes);
select a candidate structure token from the structure input sequence associated with a second amino acid position of the protein (i.e., mental processes);
predict candidate structure token results associated with the second amino acid position of the protein (i.e., mental processes and mathematical concepts); and
compare the predicted candidate structure token results to the candidate structure token (i.e., mental processes).
The abstract ideas recited in the claims are evaluated under the broadest reasonable interpretation (BRI) of the claim limitations when read in light of and consistent with the specification. As noted in the foregoing section, the claims are determined to contain limitations that can practically be performed in the human mind with the aid of a pen and paper (e.g. selecting property candidates from the plurality of candidates for the property), and therefore recite judicial exceptions from the mental process grouping of abstract ideas. Additionally, the recited limitations that are identified as judicial exceptions from the mathematical concepts grouping of abstract ideas (e.g., using a machine learning model to predict a plurality of candidates for a property of a selected amino acid position included in the second portion of the sequence of the protein that is masked) are abstract ideas irrespective of whether or not the limitations are practical to perform in the human mind. Furthermore, a law of nature correlating a genotype-phenotype association is identified at Eligibility Step 2A: Prong One.
Therefore, claims 1-20 recite an abstract idea and a law of nature.
[Step 2A Prong One: YES]
Eligibility Step 2A Prong Two: In determining whether a claim is directed to a judicial exception, further examination is performed that analyzes if the claim recites additional elements that when examined as a whole integrates the judicial exception(s) into a practical application (MPEP 2106.04(d)). 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. The claimed additional elements are analyzed to determine if the abstract idea is integrated into a practical application (MPEP 2106.04(d)(I); MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the abstract idea, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d)(III)).
The judicial exceptions identified in Eligibility Step 2A Prong One are not integrated into a practical application because of the reasons noted below.
Dependent claims 2-10, 12, 14, 15, and 17 do not recite any elements in addition to the judicial exception, and thus are part of the judicial exception.
The additional elements in independent claims 1, 13, and 20 include:
receiving at least a first portion of a sequence of a protein, wherein the protein has a second portion of the sequence that is unknown (claims 1, 13, and 20) (i.e., receiving data);
one or more processors (claim 13);
a memory coupled to at least one of the one or more processors (claim 13);
a non-transitory computer readable storage medium (claim 20);
physically synthesizing the protein having the discovered properties of the second portion of the sequence determined using the machine learning model including by identifying and assembling specific component amino acids corresponding to the unmasked properties at the respective specific amino acid positions of the second portion of the sequence into the protein (claim 1);
outputting instructions to effect a physical synthesis of the protein having the discovered properties of the second portion of the sequence determined using the machine learning model including by causing a physical assembly of specific component amino acids corresponding to the unmasked properties at the respective specific amino acid positions of the second portion of the sequence into the protein (claim 13) (i.e., outputting data); and
outputting instructions for causing a physical synthesis of the protein having the discovered properties of the second portion of the sequence determined using the machine learning model including by causing assembly of specific component amino acids corresponding to the unmasked properties at the respective specific amino acid positions of the second portion of the sequence into the protein (claim 20) (i.e., outputting data).
The additional elements in dependent claims 11, 16, 18, and 19 include:
providing the structure input sequence to the machine learning model (claims 11 and 18) (i.e., inputting data); and
the one or more processors (claims 16, 18, and 19).
The additional elements of one or more processors (claims 13, 16, 18, and 19); a memory coupled to at least one of the one or more processors (claim 13); and a non-transitory computer-readable storage medium (claim 20); invoke a computer and/or computer-related components merely as tools for use in the claimed process, and therefore are not an improvement to computer functionality itself, or an improvement to any other technology or technical field, and thus, do not integrate the judicial exceptions into a practical application (MPEP 2106.04(d)(1)).
The additional elements of receiving data (claims 1, 13, and 20); inputting data (claims 11 and 18); and outputting data (claims 13 and 20); are merely pre-solution or post-solution activities used in the claimed process – nominal additions to the claims that do not meaningfully limit the claims, and therefore do not add more than insignificant extra-solution activity to the judicial exceptions (MPEP 2106.05(g)).
The additional element of synthesizing a protein having discovered properties (claim 1), does not amount to more than mere instructions to implement an abstract idea (i.e., do not amount to more than a recitation of the words “apply it” (or an equivalent)). The additional element must do more than simply state the judicial exception (i.e., having the discovered properties) while adding the words equivalent to “apply it” (i.e., physically synthesizing the protein) (see MPEP 2106.05(f)).
Thus, the additionally recited elements merely invoke a computer and/or computer related components as tools; and/or amount to insignificant extra-solution activity; and/or do not amount to more than mere instructions to implement an abstract idea; and as such, when all limitations in claims 1-20 have been considered as a whole, the claims are deemed to not recite any additional elements that would integrate a judicial exception into a practical application, and therefore claims 1-20 are directed to an abstract idea (MPEP 2106.04(d)).
[Step 2A Prong Two: NO]
Eligibility Step 2B: Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are probed for a specific inventive concept. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they amount to significantly more than the judicial exception (MPEP 2106.05A i-vi).
The claims do not include any additional elements that are sufficient to amount to significantly more than the judicial exception(s) because of the reasons noted below.
Dependent claims 2-10, 12, 14, 15, and 17 do not recite any elements in addition to the judicial exception(s).
The additional elements recited in independent claims 1, 13, and 20 and dependent claims 11, 16, 18, and 19 are identified above, and carried over from Step 2A: Prong Two along with their conclusions for analysis at Step 2B. Any additional element or combination of elements that was considered to be insignificant extra-solution activity at Step 2A: Prong Two was re-evaluated at Step 2B, because if such re-evaluation finds that the element is unconventional or otherwise more than what is well-understood, routine, conventional activity in the field, this finding may indicate that the additional element is no longer considered to be insignificant; and all additional elements and combination of elements were evaluated to determine whether any additional elements or combination of elements are other than what is well-understood, routine, conventional activity in the field, or simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception, per MPEP 2106.05(d).
The additional elements of one or more processors (claims 13, 16, 18, and 19); a memory coupled to at least one of the one or more processors (claim 13); a non-transitory computer-readable storage medium (claim 20); receiving data (claims 1, 13, and 20); inputting data (claims 11 and 18); and outputting data (claims 13 and 20); are conventional (see MPEP at 2106.05(b) and 2106.05(d)(II) regarding conventionality of computer components and computer processes).
The additional element of synthesizing a protein (claim 1); is conventional. Evidence for the conventionality is shown by Pereira et al. (Protein Science, 2021, Vol. 30, pp. 1502-1520, as cited in the Office action mailed 18 December 2024). Pereira et al. reviews recent milestones in the step-by-step design of proteins for small molecule interaction (Title; and Abstract), and shows various aspects pertaining to designing a protein sequence (e.g., Section 5: pp. 1513-1515) utilizing machine-learning algorithms for fast screening of the universe of possibilities for the identity of each amino acid in the designed protein (page 1513, column 1, para. 2), and further shows aspects pertaining to synthesizing the designed protein (Section 6: pp. 1515-1516) such as the last step of a protein design study is the correct synthesis of the computationally defined sequences (page 1515, para. 2).
Therefore, when taken alone, all additional elements in claims 1-20 do not amount to significantly more than the above-identified judicial exception(s). Even when evaluated as a combination, the additional elements fail to transform the exception(s) into a patent-eligible application of that exception. Thus, claims 1-20 are deemed to not contribute an inventive concept, i.e., amount to significantly more than the judicial exception(s) (MPEP 2106.05(II)).
[Step 2B: NO]
Response to Arguments
The Applicant’s arguments/remarks received 07 November 2025 have been fully considered, but are not persuasive.
The Applicant states on page 9 (para. 3) of the Remarks that the Office has analyzed the claims a generic, linear, and “single pass” mental process summarized as “predict, evaluate, select” while failing to appreciate, or altogether ignoring, the specific, non-mental, and technically-grounded iterative search architecture that is explicitly claimed and described in the claim. The Applicant further states (para. 4) that the background of the application identifies a specific, well-known technical problem in the field of computational biology: conventional protein structure prediction model, which are computed with a single pass of a conventional feed-forward network, possess a critical flaw…that they “do not offer an opportunity for improvement even with additional compute resources.” The Applicant further states that this establishes a clear technical problem, and that the claims provide a technical solution of an iterative search architecture that uses the machine learning model in a novel, multi-step feedback loop, and that this claimed architecture is designed to apply additional compute resources to produce improved results and discover a more optimal protein structure that exceeds the initial results of a single pass model, and therefore this is an improvement to the function of the computational system itself. The Applicant further states (para. 5) that the Office’s analysis fails at every stage of the Alice/Mayo framework, because it incorrectly identifies a “mental process” where none exists, it dismisses the specific technical architecture as “generic,” and it treats a transformative physical step as mere “insignificant extra-solution activity.”
These arguments are not persuasive, because first, with regard to the Applicant’s statement that the background of the application identifies a specific, well-known technical problem in the field of computational biology: conventional protein structure prediction model, which are computed with a single pass of a conventional feed-forward network, possess a critical flaw…that they “do not offer an opportunity for improvement even with additional compute resources”, it is noted that model architectures existed at the effective filing date of the claimed invention that contrast with “a single pass of a conventional feed-forward network” – e.g., model architectures such as a recurrent neural network (RNN), which utilize feedback loops to allow information to persist, and data to “cycle back”, making RRNs suitable for sequential data like text, time series, or even protein sequences. It is further noted that the amended instant independent claims do not appear to explicitly recite any particular type of machine learning architecture, e.g., it appears that the broadest reasonable interpretation of amended claim 1 could even comprise using a single-pass feedforward network, either by feeding the output back into the same model, or by using a modular feedforward network (i.e., a collection of individual single-pass feedforward networks working together to achieve a final, combined output). Second, the amended claims do not recite any additional elements beyond conventional computer and/or computer related components that merely used to perform the model’s calculations, and therefore the claims do not provide for “an improvement to the function of the computational system itself” as argued. Third, the above rejection identifies multiple claim limitations as reciting a mental process and/or a mathematical concept because the broadest reasonable interpretation of the claim limitations are steps in a model algorithm that are either mathematical and/or practical to perform in the human mind with the aid of pen and paper. Fourth, the Applicant’s foregoing argument encompasses elements that are incident to the very nature of machine-learning, i.e., “an iterative search architecture,” and a “multi-step feedback loop”. Fifth, the additional element of synthesizing a protein was not identified as mere “insignificant extra-solution activity” as alleged, but rather, identified as not amounting to more than mere instructions to implement an abstract idea, as discussed in the rejection of record and in the above rejection.
The Applicant states on page 10 (para. 1) of the Remarks that the claims are not directed to a judicial exception, and that the Office action rejection begins with the finding that the claims are directed to two judicial exceptions: an abstract idea (specifically, mental processes and mathematical concepts) and a law of nature. The Applicant further states that the claims do not recite a mental process or a law of nature, but rather, they involve complex, non-mental computation to achieve a specific, technical outcome. The Applicant further states (para. 2) that the claimed process cannot practically be performed in the human mind, a specific and binding carve-out delineated in the USPTO guidance memorandum dated August 4, 2025 on subject matter eligibility. The Applicant further states (para. 3) that the Office action states that “the amount of data and/or the amount of time to perform the process steps, in and of themselves is not a limitation which takes a process out of the realm of the human mind,” and further states that this statement is in direct contradiction to the explicit instructions provided in the Memorandum that states “A claim does not recite a mental process when it contains limitation(s) that cannot practically be performed in the human mind, for instance when the human mind is not equipped to perform the claim limitation(s)… Examiners are reminded not to expand this grouping… Claim limitations that encompass AI in a way that cannot be practically performed in the human mind do not fall within this grouping.” The Applicant further states that the claims involve high-dimensional prediction, iterative, multi-set re-prediction, complex computational evaluation, and iterative refinement, and this is a process that is impractical to perform in the human mind not merely because it is “fast” but because its kind and quality of computation are entirely outside the capabilities of the human mind.
These arguments are not persuasive, because first, the USPTO guidance memorandum dated August 4, 2025 on subject matter eligibility, explicitly states that the memorandum is not intended to announce any new USPTO practice or procedure and is meant to be consistent with existing USPTO guidance, and that Examiners should consult the specific MPEP sections for more thorough information. Accordingly, the Office actions of record and the present Office action were prepared in accordance with the guidance set forth in the MPEP. Second, the Applicant’s assertion that “the claims involve high-dimensional prediction, iterative, multi-set re-prediction, complex computational evaluation, and iterative refinement, and this is a process that is impractical to perform in the human mind not merely because it is ‘fast’ but because its kind and quality of computation are entirely outside the capabilities of the human mind” is not aligned with the broadest reasonable interpretations of the instant claims as amended, e.g., amended claim 1 only broadly recites “using a machine learning model to predict a plurality of candidates for a property of a selected amino acid position…” which does not recite any particular aspects of the model architecture that would take the process of using the model out of the realm of the human mind.
The Applicant states on page 10 (para. 4) of the Remarks that the Office presents an alternative allegation, that the claims are directed to a law of nature by associating genomic data… with phenotypes… i.e., a genotype-phenotype correlation. The Applicant further states that the claims are not directed to the mere recitation of a law of nature, but rather to a specific way of using it, and further states that the Office’s alternative allegation attempts to reduce the entire claimed invention to “thinking about a natural law.” The Applicant further states on page 11 (para. 1) that this reductionist approach is precisely what the “directed to” inquiry, and specifically Prong Two of the MPEP analysis, is designed to prevent. The Applicant further states that the claims are not directed to the mere existence of a correlation between an amino acid sequence (genotype) and a protein’s properties (phenotype), and this correlation is, at best, a scientific principle that is involved in the subject matter and used by the claims, and that the claims, when considered as a whole, is not on the law itself, but on a specific, non-conventional, and technically-advanced computational method for discovering an optimal protein in a useful, targeted, and non-obvious way. The Applicant further states that the claims are directed to a practical application of that scientific principle to solve a technical problem, namely, discovering a specific, optimal protein structure that a conventional single pass model could not.
These arguments are not persuasive, because first, regarding the Applicant’s assertion that the Office’s alternative allegation attempts to reduce the entire claimed invention to “thinking about a natural law,” is noted that at Eligibility Step 2A: Prong One, examiners evaluate whether the claim recites a judicial exception, i.e., whether a law of nature, natural phenomenon, or abstract idea is set forth or described in the claim. While the terms "set forth" and "described" are thus both equated with "recite", their different language is intended to indicate that there are two ways in which an exception can be recited in a claim. For instance, the claims in Diehr, 450 U.S. at 178 n. 2, 179 n.5, 191-92, 209 USPQ at 4-5 (1981), clearly stated a mathematical equation in the repetitively calculating step, and the claims in Mayo, 566 U.S. 66, 75-77, 101 USPQ2d 1961, 1967-68 (2012), clearly stated laws of nature in the wherein clause, such that the claims "set forth" an identifiable judicial exception. Here, the instant claims are directed to protein structure prediction to identify a corresponding protein property result (e.g., structure) that aligns with a provided protein sequence. It is well established that there exists a strong natural correlation between an amino acid sequence (i.e., primary sequence) and its resulting secondary structure (e.g., α-helices, β-sheets, or turns) and that specific amino acids possess conformational preferences or “propensities” that favor certain structures, as determined by their chemical properties and backbone angles. Second, the instant claims are determined to be directed to a law of nature because the claims do not recite any additional elements that apply, rely on, or use the judicial exceptions in a manner that imposes a meaningful limit on the judicial exception, i.e., stated a different way, only if a claim recites a judicial exception and does not integrate that exception into a practical application is the claim found to be “directed to” a judicial exception, at which point the eligibility analysis would proceed to Step 2B and the search for an inventive concept. Third, with regard to the Applicant’s argument that the claims “solve a technical problem, namely, discovering a specific, optimal protein structure that a conventional single pass model could not,” it is noted that the improvement can be found in the judicial exception(s) alone, and therefore the Step 2A Prong Two analysis considers the claim as a whole. That is, the limitations containing the judicial exception as well as the additional elements in the claim besides the judicial exception are evaluated together to determine whether the claim integrates the judicial exception(s) into a practical application, e.g., by considering the way in which the additional elements use or interact with the exception, such that the additional elements may integrate the exceptions into a practical application. Here, the asserted technical problem lies with the model itself, which is identified as a judicial exception at Step 2A Prong One (and alone cannot provide the improvement at 2A Prong Two), and that is not integrated into a practical application at Step 2A Prong Two because there are no additional elements identified that apply, rely on, or use the judicial exceptions in a manner that imposes a meaningful limit on the judicial exception when the claims are considered as a whole.
The Applicant states on page 11 (para. 2) of the Remarks that even if the claims were found to recite a judicial exception, the rejection would still fail at MPEP Step 2A, Prong 2. The Applicant further states that as established in the background of the application, the existing technology is the conventional feed-forward network which is limited to a single pass and does not offer an opportunity for improvement even with additional compute resources, and further states that the claims recite a specific computational architecture that improves this existing technology, because it recites a non-generic, multi-step iterative feedback loop. The Applicant further states that this is a particular solution that improves the existing technology, and is not just using the machine learning model as a tool as it is a novel way of using a machine learning model in an iterative search framework to achieve a technically superior result that the conventional single pass cannot.
These arguments are not persuasive, because first, and as noted in the foregoing responses to arguments and in the above rejection, the asserted technical problem and purported improvement lies with the model itself, which is identified as a judicial exception at Step 2A Prong One (and alone cannot provide the improvement at 2A Prong Two), and that is not integrated into a practical application at Step 2A Prong Two because there are no additional elements identified that apply, rely on, or use the judicial exceptions in a manner that imposes a meaningful limit on the judicial exception when the claims are considered as a whole.
The Applicant states on page 11 (para. 3) of the Remarks that even in the recent precedential decision In re Desjardins, the ARP vacated the rejection because the Desjardins claims recited a technical improvement to the function of the AI model itself, specifically, “protecting knowledge about previous tasks” and “reduc[ing] system complexity”). The Applicant further states that the present claims also recite a technical improvement to the function of the AI system, because they transform the system from a static “single pass” predictor (the flawed “existing technology”) into a dynamic, iterative search tool that “exceed[s] the initial results” and finds a “more optimal” solution.
These arguments are not persuasive, because first, with regard to the Applicant’s attempt to analogize the instant claims to the claims in Desjardins, these arguments are not persuasive at least because the fact patterns differ between the claims at issued in Desjardins and the instant claims, not least in that the “ARP” in Desjardins notes that the Federal Circuit held that the eligibility determination should turn on whether “the claims are directed to an improvement to computer functionality versus being directed to an abstract idea” (citing Enfish), prior to the “ARP” finding that the improvement to how the machine learning model operates allows artificial intelligence (AI) systems to use less of their storage capacity and enables reduced system complexity, as supported by the Specification – i.e., the improvement to the model provided an improvement to computer functionality itself. This fact pattern contrasts with the fact pattern of the instant claims, at least because the instant claims merely invoke a computer and/or computer related components as tools for using a machine learning model to search for properties of a protein using amino acid sequence data as input to the model.
The Applicant states on page 12 (para. 1) of the Remarks that the physically synthesizing step is a meaningful, transformative, and non-conventional step, and therefore, in the alternative, even if the claims were found to be directed to a judicial exception and to lack a practical application in Step 2A, the claims are nonetheless patent-eligible because they recite an inventive concept that amounts to significantly more than the alleged exception, thereby satisfying Alice/Mayo Step 2B, because the “physically synthesizing” step is a meaningful, transformative, and non-conventional step. The Applicant further states (para. 2) that this step is not merely “apply it,” but rather, it is the physical culmination and transformation of the entire inventive process. The Applicant further states that the claims recite an integrated approach that begins with abstract data (a masked sequence) and, through the inventive iterative discovery process, concludes with the creation of a specific, tangible, and useful physical article of a novel protein. The Applicant further states that this is a clear “transformation or reduction of a particular article to a different state or thing, because the “articles” are the “component amino acids,” and they are “transformed” from individual components into a new “different… thing,” which is the “protein” itself. The Applicant further states that the Office action argues that this is not a transformation because “any specific amino acid itself is still the same amino acid molecule.” The Applicant further states that by this logic, building a new, specific, and useful machine from “conventional” nuts and bolts would not be a “transformation” because the nuts and bolts remain nuts and bolts. The Applicant further states that this is contrary to conventional logic, and further that the synthesis step is not an “insignificant extra-solution activity” as it is the physical purpose of the computational discovery, and that the computational steps are meaningfully limited by this physical step, which integrates the abstract discover into a concrete, physical, and transformative application.
These arguments are not persuasive, because first, the phrase "meaningful limitations" has been used by the courts even before Alice and Mayo in various contexts to describe additional elements that provide an inventive concept to the claim as a whole. The considerations described in MPEP § 2106.05(a)-(d) are meaningful limitations when they amount to significantly more than the judicial exception, or when they integrate a judicial exception into a practical application. This broad label signals that there can be other considerations besides those described in MPEP § 2106.05(a)-(d) that when added to a judicial exception amount to meaningful limitations that can transform a claim into patent-eligible subject matter. However, the claim should add meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment to transform the judicial exception into patent-eligible subject matter (MPEP 2106.05(e)) and should amount to more than a recitation of the words "apply it" (or an equivalent, e.g., synthesize the protein) and generally reciting only the idea of a solution or outcome, i.e., failing to recite details of how a solution to a problem is accomplished (MPEP 2106.05(f)). Second, regarding the Applicant’s argument that the inventive iterative discovery process concludes with the creation of a specific, tangible, and useful physical article of a novel protein, it is noted that the instant claims do not actually recite the creation of a “specific, tangible, and useful physical article of a novel protein,” but rather the idea of said creation. Third, it is noted that neither the rejection of record nor the above rejection determine that the synthesis step is an “insignificant extra-solution activity” as alleged in the foregoing argument, but rather, the synthesis step is at least identified as mere instructions to implement an abstract idea, as previously discussed. Fourth, regarding the Applicant’s argument that the synthesis step is a clear “transformation or reduction of a particular article to a different state or thing, because the “articles” are the “component amino acids,” and they are “transformed” from individual components into a new “different… thing,” which is the “protein” itself, it is noted that the MPEP at 2106.05(c) (para. 5) that changing to a different state or thing usually means more than simply using an article changing the location of an article (e.g., Tilghman v. Proctor, 102 U.S. 707 (1881), provides an example of effecting a transformation of a particular article to a different state or thing. In that case, the claim was directed to a process of subjecting a mixture of fat and water to a high degree of heat and included additional parameters relating to the level of heat, the quantities of fat and water, and the strength of the mixing vessel. The claimed process, which used the natural principle that the elements of neutral fat require that they be severally united with an atomic equivalent of water in order to separate and become free, resulted in the transformation of the fatty bodies into fat acids and glycerine. Fifth, regarding the Applicant’s misconstrued analogy of building a new, specific, and useful machine from “conventional” nuts and bolts, it noted that building a machine from conventional nuts and bolts would not be considered a particular transformation in accordance with MPEP 2106.05(c) because it would merely involve “using” and “changing the location” of the articles (i.e., nuts and bolts) according to the structural blueprint for the machine.
The Applicant states on page 12 (para. 3) of the Remarks that with respect to the reliance on Pereira et al. to prove “conventionality”, the Office action has improperly dissected the claim. The Applicant further states that the claim as a whole recites a process of iterative computational discovery followed by synthesis, and that the Office action provides no evidence that the entire, integrated process of the claim is conventional. The Applicant further states that more importantly, the article being synthesized is not conventional, because it is a new composition of matter whose sequence and properties were discovered by the preceding inventive iterative process. The Applicant further states that the synthesis step is not a generic activity as it is the specific synthesis of the non-conventional protein that was just discovered by the preceding steps. The Applicant further states on page 13 (para. 1) that claim 1 has been amended to recite physically synthesizing the protein having the discovered properties of the second portion of the sequence determined using the machine learning model including by “identifying” and assembling “specific” component amino acids “corresponding to the unmasked properties at the respective specific amino acid positions of the second portion of the sequence into the protein.” The Applicant further states that in the amended claim “unmasked properties” are not merely related to the synthesis but are the mechanistic inputs that define the physical act, and further that the synthesis is performed by identifying and assembling amino acids corresponding to the unmasked properties. The Applicant further states that the “unmasked properties” are now recited as directly affecting and governing the physical synthesis, and that they are the blueprint that dictates which specific component amino acids are to be identified and assembled, and where (e.g., “at the respective specific amino acid positions”). The Applicant further states that the amended claim ties the computational result directly to the specific physical building blocks of the manufacturing process, and that this is the very definition of integration, and MPEP 2106.04 states that a claim integrates an exception when it “apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception” and that here, the physical step is the “meaningful limit.” The Applicant further states that the claim is not directed to “discovering properties” in a vacuum as it is limited to a process that culminates in, and is defined by, the physical manufacture of the specific protein molecule that embodies those properties.
These arguments are not persuasive, because first, the consideration of conventionality is only evaluated at Step 2B of the eligibility analysis, i.e., the search for an inventive concept, and an "inventive concept" is furnished by an element or combination of elements that is recited in the claim in addition to (beyond) the judicial exception, and is sufficient to ensure that the claim as a whole amounts to significantly more than the judicial exception itself. Therefore, the Applicant’s argument that “the claim as a whole recites a process of iterative computational discovery followed by synthesis, and that the Office action provides no evidence that the entire, integrated process of the claim is conventional” is an argument that is not consistent with guidance provided at Step 2B (MPEP 2106.05). Second, regarding the Applicant’s argument that “the article being synthesized is not conventional, because it is a new composition of matter whose sequence and properties were discovered by the preceding inventive iterative process,” it is reiterated that the claims do not actually recite a particular composition of matter, much less a particular protein. Third, regarding the Applicant’s argument that “the ‘unmasked properties’ are now recited as directly affecting and governing the physical synthesis, and that they are the blueprint that dictates which specific component amino acids are to be identified and assembled, and where (e.g., ‘at the respective specific amino acid positions’),” it is reiterated that the claims do not actually recite specific amino acids, much less a particular sequence of amino acids to generate a particular protein. Fourth, regarding the Applicant’s argument that “the claim is not directed to ‘discovering properties’ in a vacuum as it is limited to a process that culminates in, and is defined by, the physical manufacture of the specific protein molecule that embodies those properties,” it is again reiterated that the claims do not recite synthesizing a particular protein, but rather merely recite the idea of synthesizing a protein having discovered properties that are not defined by the claim.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/S.W.B./Examiner, Art Unit 1687
/Joseph Woitach/Primary Examiner, Art Unit 1687