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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02 April 2026 has been entered.
Status of the Claims
Claims 16, 19-20, 23, 25-26, and 31-36 are examined herein.
Claims 1-15, 17-18, 21-22, 24, and 27-30 are canceled.
Priority
As detailed on 18 May 2021 filing receipt, the application claims priority as early as 20 July 2018. At this point in examination, all claims have been interpreted as being accorded this priority date as the effective filing date.
Declarations Under 37 CFR 132
The affidavit by Catherine Etchebest was filed 02 April 2026. The substance of the affidavit will be responded to in the remarks.
Withdrawn Rejections
The rejection under 35 USC 112(a) is withdrawn in view of amendment which no longer requires constructing a variant, which is consistent with the applicant remarks (pg. 15, Section I) and the 29 January 2026 Patent Trial and Appeal Board decision (2025-002246).
The rejection under 35 USC 103, in view of the aforementioned PTAB decision reversing rejection, is withdrawn.
The following rejections and/or objections are either maintained or newly applied. They constitute the complete set applied to the instant application.
Claim Rejections - 35 USC § 112(b)
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 16, 19-20, 23, 25-26, and 31-36 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.
Claims 16 and 35-36 recite, in their first limitations, a protein database which includes at least one index of numerical values and “several indexes.” Therefore, it is unclear whether at least one index or at least two indexes is required to perform the required steps. Claims 19-20, 23, 25-26, and 31-34 are dependent on these claims and rejected on similar grounds.
Claims 16 and 36 recite lists with unclear relationships among list elements. Claim 1 recites “comparing,” “predicting,” and “selecting” steps not joined by a conjunction such as “and” or “or.” Claims 19-20, 23, 25-26, and 31-34 are dependent on claim 1 and rejected on similar grounds. For compact examination, it is assumed the claims will be amended to recite an “and” after the “predicting” step.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 35 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 35 is amended to recite “an index selection module.” However, such a module does not occur in the specification and thus the term is considered to lack written description support.
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 16, 19-20, 23, 25-26, and 31-36 are rejected under 35 USC § 101 because the claimed inventions are directed to non-statutory subject matter. "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 "predicting at least one fitness value of a protein."
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 a method (claims 16, 19-20, 23, 25-26, 31-34, and 36) and a system (claim 35), 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)).
Claims 16 and 34-36 recite selecting an index from a protein database, where making a selection is a step the human mind is practically equipped to perform and thus a mental step.
Claims 16 and 34-36 recite calculating elementary numerical sequences and applying a Fast Fourier Transform. The calculating could be a mathematical concept in the form of a numerical calculation or a mental step of appending numbers together, which the human mind could feasibly do. The Fast Fourier Transform is a verbal description an algorithm applied to numerical data and thus a mathematical concept.
Claims 16 and 34-36 recite determining an extended numerical sequence by concatenating numerical sequences, where concatenation may be understood as a mathematical concept of joining numbers or as a mental step of combining items.
Claims 16 and 34-36 recite comparing sequences with a reference sequence. Making a comparison is a step the human mind is practically equipped to perform and thus a mental step.
Claims 16 and 34-36 recite predicting a fitness value by determining a fitness spectrum value in the database closest to the variant spectrum, which is interpreted as amounting to comparison to reference values and thus a step the human mind can practically perform.
Claims 16, 34, and 36 recite making a selection based on which predicted fitness value is closest to the desired fitness value, where making a selection is a step the human mind is practically equipped to perform and thus a mental step.
Claim 19 recites further details of the calculation, which is previously discussed as a mathematical step.
Claim 20 recites the mathematical equation upon which each elementary protein spectrum depends and as such is a mathematical concept.
Claim 23 recites further details of the calculation of the sequence and application of the Fast Fourier Transform, which are previously discussed as a mathematical steps.
Claim 25 recites the mathematical equation for determining the root mean square error and as such is a mathematical concept.
Claim 26 recites the mathematical equation for determining the coefficient of determination for each index and as such is a mathematical concept.
Claim 31 recites additional information related to the indices which are information stored in the database, and information or “data per se” as not being directed to any statutory category. MPEP 2106.03(I) pertains.
Claim 32 recites additional information about the categories of indexes being relation to statistical features and thus is information in a database. Information or “data per se” as not being directed to any statutory category. MPEP 2106.03(I) pertains.
Claim 33 recites comparing comprising identifying the closest to a reference and so is further limiting the abstract mental step of comparison.
Hence, the claims explicitly recite numerous elements that, individually and in combination,
constitute abstract ideas. The claims must therefore be examined further to determine whether they
integrate that abstract idea into a practical application (MPEP 2106.04(d)). [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))?
The following elements in addition to the abstract ideas are recited by the claims: a protein database (claims 16 and 34-36), a predetermined database of reference extended numerical values (claims 16 and 34-36), a non-transitory computer-readable medium (claim 34), and a memory and processor comprising a system (claim 35).
The claims are interpreted as amounting to accessing stored information in databases and analyzing the data using a general purpose computer. Specific computational steps by which the computer, or recited "memory and a processor," 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)).
None of the dependent claims recite any additional non-abstract elements; they are all directed
to further aspects of the information being analyzed, the manner in which that analysis is performed, or
the mathematical operations performed on the information.
Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims are directed to that abstract idea. Claims that are directed to abstract ideas must be examined further to determine whether the additional elements besides the abstract idea render the claims significantly more than the abstract idea. Claims that are directed to abstract ideas and that raise a concern of preemption of those abstract ideas must be examined to determine what elements, if any, they recite besides the abstract idea, and whether these additional elements constitute inventive concepts that are sufficient to render the claims significantly more than the abstract idea (MPEP 2106.05). [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. An inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
The following elements in addition to the abstract ideas are recited by the claims: a protein database (claims 16 and 34-36), a predetermined database of reference extended numerical values (claims 16 and 34-36), a non-transitory computer-readable medium (claim 34), and a memory and processor comprising a system (claim 35).
Use of the database, interpreted as storing and retrieving information in memory, is a conventional computer activity (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)(II) pertains. Additionally, instructions to implement an abstract idea on a computer do not provide significantly more (MPEP 2106.05(A)(i)).
When the claims are considered as a whole, they do not integrate the abstract idea into a
practical application; they do not confine the use of the abstract idea to a particular technology; they do
not solve a problem rooted in or arising from the use of a particular technology; they do not improve a
technology by allowing the technology to perform a function that it previously was not capable of
performing; and they do not provide any limitations beyond generally linking the use of the abstract
idea to a broad technological environment (i.e. computerized data analysis). See MPEP 2106.05(a) and
2106.05(h). [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.
Response to the 02 April 2026 Applicant Remarks
Applicant remarks state the amended claims are fundamentally different from the previously filed claims because they are “anchored to a real, measurable physical or chemical property of a real amino acid” and “index selection is anchored to real experimental data” (pg. 18, first paragraph). It is unclear why these step are fundamentally different as they are still considered to be mental and mathematical data analysis steps based on stored information. The candidate values being based on amino acid properties or experimental data is still mere data, and collection of the data experimentally is not required. Therefore, the relationship to a nexus in the real world is considered to be limited.
Applicant remarks state, regarding Step 2A Prong One of 101 analysis, that the amended claims do not recite mental steps, where the stated steps are encoding amino acid sequences, applying a Fast Fourier Transform, concatenating spectra, and comparing the results (pg. 17, third paragraph). An encoding step is not clearly recited by the claims; the claims recite encoded amino acid sequences are in a database. If the encoding refers to the calculating numerical sequences, this is not clearly limited to a mathematical step, as it can be interpreted on comparing values on to a table of value (that is, what value for a property an amino acid would have in an index), which the human mind can do, though it may also be mathematical. The Fourier transform is a mathematical concept, as disclosed by the remarks as “iterative complex-number arithmetic.” It is unclear how comparing the sequences could not be a mental step. The claims require comparing, which is a mental step similar to evaluation and judgment (MPEP 2106.04(a)(2)(III). However, if the comparison is done mathematically, it would still be an abstract step.
Applicant remarks state, regarding Step 2A Prong Two of 101 analysis, that the instant claims provide a specific technological improvement to the field of protein engineering (pg. 19, last paragraph) and the alleged improvement being increased accuracy compared to similar methods (pg. 20, second paragraph). This argument is unpersuasive for two reasons. First, no protein is being engineered as part of this process, where protein engineering – or synthesis – is a technological field. Second, it is unclear what technology is being improved upon in the instant claims because the claimed technological limitations in the claims – databases, memory, and processors – amount to a general purpose computer. Any alleged improvement is provided by the abstract steps. Instructions to apply the abstract idea using a computer does not integrate that abstract idea into a practical application (see MPEP 2106.04(d) § I; and MPEP 2106.05(f)).
Continuing on this topic, applicant remarks allege similarity to McRO and Thales Visionix for eligibility of the instant claims. The analogy to these decisions is unpersuasive. Regarding McRO, applicant remarks state “the specific rules relating amino acid property indexes to FFT-derived protein spectra, combined according to a defined concatenation pattern drawing from distinct property categories, provide a technological improvement over existing protein fitness prediction techniques” (pg. 20, third paragraph). However, unlike McRO, these specific rules do not result in an improved technological result; the claims are directed to data analysis, and the additional elements – here considered to be conventional computer elements – do not integrate the abstract ideas into a practical application in the form of an improvement because they are interpreted as applying the abstract ideas using a computer. It is also noted that argument for similarity of McRO was not persuasive in the decision of the Patent Trial and Appeal Board. Regarding Thales Visionix, the specific physical configuration of elements in addition to the abstract ideas was important to patent eligibility (pg. 21, last paragraph to pg. 22, first paragraph). Here, the chemical encodings being dictated by protein structure does not require an element in addition to the abstract ideas because no data is being collected from proteins themselves. The claims begin and end with data, and thus only the generic computer is regarded as an element in addition to the abstract ideas, and applying the abstract ideas using a computer does not integrate abstract ideas into a practical application.
Applicant remarks point to Ex Parte Desjardins and draws analogy in the form of “improv[ing] how computational protein analysis operates - enabling accurate fitness prediction across combinatorial
mutation spaces that were previously intractable to computational methods” (pg. 22, second paragraph). However, the improvement in Desjardins is directed to the computer, whereas the alleged improvement in the instant claims is directed to abstract ideas, namely selecting a protein.
Applicant remarks state the claims provide an alleged improvement to the concrete technology of computational protein engineering (pg. 22, last paragraph) and produce concrete, experimentally verified results in the physical world (pg. 23, last paragraph). This argument is not persuasive because no protein is being engineered as part of this process, where protein engineering – or synthesis – is a technological field and it is unclear what technology is being improved upon in the instant claims because the claimed technological limitations in the claims – databases, memory, and processors – amount to a general purpose computer. The remarks state the claims enable identification of variants that actually work and could not have been identified by prior methods (pg. 23, last paragraph). This speaks to the novelty of the claim, but more importantly it highlights the claims are directed to selection of a protein, which is a mental step and not a nexus in the real world.
Applicant remarks state “the present claims require FFT-based spectral transformation, multi-index concatenation from distinct property categories, and comparison in the spectral domain - operations that are fundamentally computational and cannot be performed by human inspection” (pg. 24, second paragraph). Even if this is true, measured activity is still measured numerically, as the comparison is performed by root mean square error for distance between a candidate and reference, which is a mathematical calculation as found in claim 25 and Equation 1 of the specification. However, it is unclear why comparison of the spectral waveforms is something the human mind cannot do. Regarding the generic input versus specific input, where specific inputs are purported to be specific indexes, transformation, and structural requirement. However, no data is collected by physical means; data is stored in a database and transformed mathematically for downstream analysis. The claims remain interpreted as data collection and comparison.
Regarding Step 2B of 101 analysis, applicant remarks state the instant combination of property encodings, transformation to generate protein spectra, and concatenation, and specifically their ordering from different property categories, are not conventional and thus eligible at Step 2B (pg. 25, first to third paragraphs). This argument is not persuasive because these steps are interpreted as abstract steps as discussed above, and an inventive concept cannot be furnished by an abstract idea itself (MPEP 2106.05).
For these reasons, the rejection under 35 USC 101 is maintained.
Response to Declaration Under 37 CFR 132
The declaration under 37 CFR 1.132 filed 02 April 2026 is insufficient to overcome the rejection of claims 16, 19-20, 23, 25-26, and 31-36 based upon 35 USC 101 as set forth in the last Office action because the arguments are insufficient to overcome the rejection.
The affidavit recites the use of Fast Fourier Transform captures data not previously assessed (pg. 4, last paragraph to pg. 5, first paragraph), which were experimentally validated subsequent to the filing date of the invention by producing the candidate protein (pg. 6-7), where the alleged improvement is drawn to being based on physiochemical properties and multi-index concatenation (pg. 9). The improvements are still being interpreted as rooted in abstract ideas as the construction or engineering of proteins is not recited in the claims nor supported by the specification.
It is further asserted the application of Fourier Transform cannot be performed in the human mind (pg. 10, Section VII) – and this is at least partially agreed to, as it is disclosed as a mathematical concept. It is further asserted that comparison of spectra cannot be performed mentally because the elementary sequence from which they are derived may be 150-450 amino acids in length, but this argument is not commensurate with the claims, which make no limitations for the sequence length. Furthermore, the length of the spectra for comparison does not necessarily preclude them from being interpreted mentally. While a long sequence/spectrum may take longer to analyze, duration of time to perform the analysis does not graduate it from an abstract idea into something more.
Therefore, because the required steps involve data analysis in the form of mathematical and mental steps, which do not constitute a technological improvement because any technology is considered to be a general purpose computer upon which the abstract steps are performed, and such a relationship does not integrate abstract steps into a practical application (MPEP 2105.05(f)).
In view of the foregoing, the presented evidence is unpersuasive and the rejection under 35 USC 101 is maintained.
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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/R.J.K./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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