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 .
Applicant’s amendment and response filed 8/14/2025 have been entered, and carefully considered, but is not completely persuasive.
Claims 2, 4, 12, 14, 16, 22, 26, 28-30, 32-38 are pending in this application. Claims 1, 3, 5-11, 13, 15, 17-21, 23-25, 27 and 31 have been canceled. Claims 32-38 are newly added. The claims previously identified as representing certain species have been canceled, and the election of species requirement is WITHDRAWN in view of the newly submitted amendments.
In view of the above noted withdrawal of the restriction/ election of species requirement, applicant is advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
The amendments to the specification have been entered, obviating the objections from the previous action.
This application has now issued as a US PG-Pub as US 2025/0154584 A1.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation (BRI) using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 2, 4, 12, 14, 16, 22, 26, 28-30, 32-38 is/are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea of mental steps, mathematic concepts, organizing human activity, or a natural law without significantly more.
Applicant is directed to MPEP 2106 and the Federal Register notice (FR89, no 137 (7/17/2024) p 58128-58138) for the most current and complete guidelines in the analysis of patent- eligible subject matter. The current MPEP is the primary source for the USPTO’s patent eligibility guidance.
With respect to step (1): YES. The claims are drawn to statutory categories: (computer systems, methods, and computer program products).
With respect to step (2A) (1): YES. The claims recite an abstract idea, law of nature and/or natural phenomenon. The claims recite an abstract idea of identifying a partial identity or a quantity of a polypeptide present in a sample, through the analysis of encoder assay data. The analysis of the encoding assay data generated binding identifier string data corresponding to a plurality of nucleic acid sequences from the encoder assay, using those strings to infer binding profiles and calculated probability scores for an association between binder identifiers and amino acid sequences present in a sample. (See MPEP 2106.07(a)). The claims explicitly recite elements that, individually and in combination, constitute one or more judicial exceptions (JE).
Mathematic concepts, Mental Processes or Elements in Addition (EIA) in the claim(s) include:
2. (Currently amended) A method for identifying amino acid sequences of polypeptides of a plurality of polypeptides present in a sample, the method comprising:
(EIA- preamble setting forth a method, and the goal of the method.)
(a) receiving, at one or more processors, a plurality of nucleic acid sequences generated by performing an encoding assay for the plurality of polypeptides, wherein each of the plurality of nucleic acid sequences comprises a series of encoder barcode sequences, and wherein each encoder barcode sequence of a given series of encoder barcode sequences corresponds to a binder, from a set of binders, that binds to a component of a polypeptide of the plurality of polypeptides, wherein the encoding assay comprises:
(i) contacting the plurality of polypeptides with binders of the set of binders, wherein each binder of the set is attached to a nucleic acid coding tag comprising an encoder barcode that corresponds to the binder, and wherein the set of binders comprises binders that each binds to two or more different components of the plurality of polypeptides;
(ii) following binding of a binder of the set of binders to a component of a polypeptide of the plurality of polypeptides, extending a nucleic acid recording tag associated with the polypeptide by transferring the sequence, or a complement thereof, of the encoder barcode attached to the binder to the nucleic acid recording tag;
(iii) repeating steps (i)-(ii) at least one time, thereby generating a plurality of extended nucleic acid recording tags associated with the plurality of polypeptides; and
(iv) determining nucleic acid sequences of each extended nucleic acid recording tag of the plurality of extended nucleic acid recording tags or complements thereof, thereby generating the plurality of nucleic acid sequences received at the one or more processors;
(EIA- data gathering step of receiving data, having certain properties, which was produced by a set of steps, the encoder assay. Known in the prior art [0041].)
(b) converting, using the one or more processors, each nucleic acid sequence of the plurality of nucleic acid sequences into a binder identifier string by assigning a binder identifier to each encoder barcode sequence of the series of encoder barcode sequences of the plurality of nucleic acid sequences, thereby generating a plurality of binder identifier strings corresponding to the plurality of nucleic acid sequences and each comprising a series of binder identifiers, wherein the binder identifier identifies the binder to which the encoder barcode sequence corresponds;
(Mathematic concept of encoding a series of data from the nucleotide sequence into a coded string of “binder identifiers”[0055] states this is performed by an algorithm such as Talon-LUT to look up barcodes and assign identifiers, and also accounts for sequencing errors.[0056] indicates the use of a Hidden Markov Model based algorithm, Talon HMM; [0054] Alternatively a Mental Process of observing the presence of a barcode (by matching) in a sequence read, and making a notation as to which binder identifier corresponds to that barcode, repeatedly, to generate a list of notations for each sequence read.)
(c) for each binder identifier string of the plurality of binder identifier strings, generating a plurality of peptidic reads for the binder identifier string by converting each binder identifier of the binder identifier string into one or more amino acid identifiers using a specificity profile of the binder that corresponds to the binder identifier such that
(i) each of the one or more amino acid identifiers identifies a component of the plurality of polypeptides to which the binder binds, and
(ii) each peptidic read of the plurality comprises a series of amino acid identifiers that corresponds to the binder identifier string,
wherein the specificity profile of the binder of the set of binders is determined by calculating probabilities of binding of the binder to the two or more different components to which the binder binds;
(Mathematic concept of deconvolving or decoding the binder identifiers to generate a sequence of a polypeptide and calculating probability values. [0058, 0107, 0128, 0388, 0437, 0440] performed by “the computer model” by reading the identifier strings, recognizing binder identifiers and decoding possible ways the string could have been produced, using one of two algorithmic pathways: 1) bulk analysis [0061] or 2) read-level analysis [0063] which are trained ML models)
(d) for each peptidic read of the plurality of peptidic reads, calculating a probability score that the peptidic read is generated from the binder identifier string,
wherein the probability score is calculated using probabilities for every amino acid identifier of the peptidic read to be present at its position within the peptidic read,
the probabilities obtained using the specificity profile of binders of the set of binders; and
(Mathematic concept of calculating probability scores, as detailed in the bulk analysis pathway [0061-0062] or the read level pathway (2A: top-down algorithm, or 2B: deep learning based read mapping) [0063-0069] each of which being a trained ML model.)
(e) for each binder identifier string of the plurality of binder identifier strings, selecting one or more peptidic reads within the plurality of peptidic reads generated for the binder identifier string based on the probability score for each peptidic read; and
inferring amino acid sequences of polypeptides of the plurality of polypeptides present in the sample from the selected one or more peptidic reads.
(Mental concept in a computing environment or using a computer as a tool, of observing the probability scores from step d) and making a judgement as to the amino acid sequence present for the selected read. Alternatively, a Mathematic concept of using a trained computer model as set forth in [0109-0115].)
4. (Currently amended) The method of claim 2, further comprising: for each of the plurality of binder identifier strings, filtering out peptidic reads of the one or more peptidic reads generated for the given binder identifier string based on a probability that a given peptidic read was generated from amino acid sequences of the plurality of polypeptides.
(Mathematic concept of selecting a subset of peptidic reads having a probability value that meets or exceeds a threshold, and removing or filtering reads having a probability value that do not meet the threshold value.)
12. (Previously presented) The method of claim 2, wherein the series of encoder barcode sequences comprises from 4 to 20 different encoder barcode sequences.
(EIA- data gathering step modification (modifying step (a)), limiting the number of different encoder barcodes present)
14. (Previously presented) The method of claim 2, wherein the plurality of polypeptides encoded in the plurality of nucleic acid sequences by the encoding assay comprises at least 100,000 polypeptides.
(EIA- data gathering step modification of step (a), setting a threshold for the sequences to be encoded.)
16. (Currently amended) The method of claim 2, wherein the specificity profile of each binder of the set of binders is determined by calculating probabilities of binding of the binder to the two or more different components in a reference encoding assay with predetermined polypeptide sequences.
(Mathematic concept of calculating probability values)
22. (Previously presented) The method of claim 2, wherein the one or more components of the polypeptide to which the binding moiety binds comprises a post-translation modification of at least one amino acid residue.
(EIA- data gathering modification of step (a) describing an aspect of the polypeptides in the encoder assay.)
26. (Currently amended) The method of claim 2, further comprising outputting a confidence interval for an identity of at least one polypeptide of the plurality of polypeptides.
(Mathematic concept of calculating a confidence interval.)
28. (Previously presented) The method of claim 2, wherein amino acid sequences for all polypeptides of the plurality of polypeptides are identified.
(Mathematic concept modification, setting forth repeating the calculations for all polypeptides)
29. (Previously presented) The method of claim 2, wherein the plurality of nucleic acid sequences comprises at least 100,000 nucleic acid sequences.
(EIA- data gathering step regarding the amount of data received in step (a).)
30. (Previously presented) A system comprising:
one or more processors; and
a memory communicatively coupled to the one or more processors and configured to store instructions that, when executed by the one or more processors, cause the system to perform the method of claim 2.
(EIA- describing the use of general-purpose computers for carrying out the method of claim 2)
32. (New) The method of claim 2, wherein the two or more different components of the plurality of polypeptides comprise two or more different N-terminal amino acid (NTAA) residues of polypeptides of the plurality of polypeptides.
(EIA- data gathering step modification, modifying step (a) (ii).)
33. (New) The method of claim 2, wherein in (d), the calculation of the probability score comprises multiplying the probabilities for every amino acid identifier of the peptidic read to be present at its position within the peptidic read.
(Mathematic concept modification of step (d) specifying the mathematic concept of multiplication of values.)
34. (New) The method of claim 33, wherein the two or more different components of the plurality of polypeptides comprise two or more different N-terminal amino acid (NTAA) residues of polypeptides of the plurality of polypeptides.
(Mathematic concept modification of step (d) specifying the mathematic concept of multiplication of values.)
35. (New) The method of claim 34, wherein in (d), the calculation of the probability score further comprises using probabilities of performing a cleavage of the NTAA residues of polypeptides of the plurality of polypeptides each time after extending the nucleic acid recording tags associated with the polypeptides.
(Mathematic concept modification of step (d) specifying the mathematic concept of multiplication of values.)
36. (New) The method of claim 2, wherein a list of the selected one or more peptidic reads with their calculated probabilities for each of the plurality of binder identifier strings is outputted to a user.
(EIA- routine output of data)
37. (New) The method of claim 2, wherein in (e), inferring amino acid sequences comprises performing a sequence alignment of the selected one or more peptidic reads to amino acid sequences of the plurality of polypeptides present in the sample.
(Mental concept modification of step e) utilizes alignment or matching, in a computing environment, or using a computer as a tool.)
38. (New) The method of claim 37, further comprising calculating a confidence interval for the sequence alignment results.
(Mathematic concept of calculating a confidence interval.)
With respect to step 2A (2): NO. The claims were examined further to determine whether they integrated any JE into a practical application (MPEP 2106.04(d)). The claimed additional elements are analyzed alone, or in combination to determine if the JE is integrated into a practical application (MPEP 2106.05(a-c, e, f and h)).
Claim(s) 2, 12, 14, 22, 30, 32, 36 recite the additional non-abstract element(s) of data gathering or a description of the data gathered.
Data gathering steps are not an abstract idea, they are extra-solution activity, as they collect the data needed to carry out the JE. The data gathering does not impose any meaningful limitation on the JE, or how the JE is performed. The additional limitation (data gathering) must have more than a nominal or insignificant relationship to the identified judicial exception. (MPEP 2106.04/.05, citing Intellectual Ventures LLC v. Symantec Corp, McRO, TLI communications, OIP Techs. Inc. v. Amason.com Inc., Electric Power Group LLC v. Alstrom S.A.).
Claim(s) 2, 30 recite the additional non-abstract element (EIA) of a general-purpose computer system or parts thereof.
The EIA do not provide any details of how specific structures of the computer elements are used to implement the JE. The claims require nothing more than a general-purpose computer to perform the functions that constitute the judicial exceptions. The computer elements of the claims do not provide improvements to the functioning of the computer itself (as in DDR Holdings, LLC v. Hotels.com LP); they do not provide improvements to any other technology or technical field (as in Diamond v. Diehr); nor do they utilize a particular machine (as in Eibel Process Co. v. Minn. & Ont. Paper Co.). Hence, these are mere instructions to apply the JE using a computer, and therefore the claim does not recite integrate that JE into a practical application.
Dependent claim(s) 4, 16, 26, 28, 30, 33-35, 37-38 recite(s) an abstract limitation to the JE reciting additional mathematic concepts, or mental processes. Additional abstract limitations cannot provide a practical application of the JE as they are a part of that JE.
In combination, the limitations of data gathering, for the purpose of carrying out the JE, using a general-purpose computer merely provide extra-solution activity, and fail to integrate the JE into a practical application.
With respect to step 2B: NO. The claims recite a JE, do not integrate that JE into a practical application, and thus are probed for a specific inventive concept. The judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). The additional elements were considered individually and in combination to determine if they provide significantly more than the judicial exception. (MPEP 2106.05.A i-vi).
With respect to claim(s) 2, 12, 14, 22, 30, 32, 36: The limitation(s) identified above as non-abstract elements (EIA) related to data gathering do not rise to the level of significantly more than the judicial exception.
CHEE (US 2019/0145982; specification and pto-1449) discloses performing an encoding assay and receiving the results of the encoding assay as required for claim 2. See Examples 1-25, and claims.)
CHEE 2, (US 2023/0136966, specification and pto-1449) discloses performing sequential encoding assays and receiving the results (nucleic acid sequence reads) of the assay as required for claim 2. [0056-0096, 0193-0211]
CHEE 3, (US 2023/0040363 A1, 2/9/2023) discloses spatially encoded biological array processes, and receiving the results, as required for claim 2.
SUASTEGUI (US 2023/0193248 A1 6/22/2023) discloses performing encoded assays (in particular, the ProteoCode assay), and receiving the nucleic acid sequence data as required for claim 2 (Example 10).
BRODIN (US 2023/0257801 A1, 8/17/2023) discloses performing encoded assays, [0104], and receiving the nucleic acid sequence data as required for claim 2 [0145+].
OKERBURG (US 2023/0203562 A1, 6/29/2023) discloses performing encoded assays, and receiving the nucleic acid sequence data as required for claim 2.
These elements meet the BRI of the identified data gathering limitations. As such, the prior art recognizes that this data gathering element is routine, well understood and conventional in the art (as in Alice Corp., CyberSource v. Retail Decisions, Parker v. Flook).
In the specification at [0041-0043] it is disclosed that the steps identified as data gathering can be met using prior art known methods:
[0041] sets forth using the ProteoCode® assay,
other prior art known Next-Generation-Peptide-Sequencing Assays (NGPS), or
other prior art known encoding assays “reported in… US 2019/0145982 A1 and US 2023/0136966 A1…”
and the resulting polynucleotides are sequenced using prior art known high-throughput next generation digital sequencing methods [0043].
Activities such as data gathering do not improve the functioning of a computer, or comprise an improvement to any other technical field. The limitations do not require or set forth a particular machine, they do not effect a transformation of matter, nor do they provide an unconventional step (citing McRO and Trading Technologies Int’l v. IBG). Data gathering steps constitute a general link to a technological environment. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception are insufficient to provide significantly more (as discussed in Alice Corp.,).
With respect to claims 2 and 30: the limitations identified above as non-abstract elements (EIA) related to general-purpose computer systems do not rise to the level of significantly more than the judicial exception.
Each of CHEE 1-3, SUASTEGUI, BRODIN and OKERBURG disclose computer systems or computing elements which meet the BRI of the claimed computer system or computer system elements, comprising input, output/ display, a processor, and memory.
As such, the prior art recognizes that these computing elements are routine, well understood and conventional in the art.
The specification, at [0170-0172] discloses the use of routine general-purpose computers for carrying out the invention, and/or the use of commercially available computer system elements.
These elements do not improve the functioning of the computer itself, or comprise an improvement to any other technical field (Trading Technologies Int’l v IBG, TLI Communications). They do not require or set forth a particular machine (Ultramercial v. Hulu, LLC., Alice Corp. Pty. Ltd v. CLS Bank Int’l), they do not effect a transformation of matter, nor do they provide an unconventional step. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception are insufficient to provide significantly more (as discussed in Alice Corp., CyberSource v. Retail Decisions, Parker v. Flook, Versata Development Group v. SAP America).
The specification, at [0170-0172] discloses the use of routine general-purpose computers for carrying out the invention, and/or the use of commercially available computer system elements.
Dependent claim(s) 4, 16, 26, 28, 30, 33-35, 37-38 each recite a limitation requiring additional mathematic concepts or mental processes. Additional abstract limitations cannot provide significantly more than the JE as they are a part of that JE (MPEP 2106.05).
In combination, the data gathering steps providing the information required to be acted upon by the JE, performed in a generic computer or generic computing environment fail to rise to the level of significantly more than that JE. The data gathering steps provide the data for the JE, which is carried out by the general-purpose computers. No non-routine step or element has clearly been identified.
The claims have all been examined to identify the presence of one or more judicial exceptions. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether the additional limitations integrate the judicial exception into a practical application. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether those additional limitations provide an inventive concept which provides significantly more than those exceptions. For these reasons, the claims, when the limitations are considered individually and as a whole, are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Applicant’s arguments
Applicant’s arguments have been carefully considered but are not completely persuasive.
Applicant argues the categorization or identification of abstract ideas, and/or a natural law in the claims. The Examiner has specifically identified each limitation in the claim, and what category of judicial exception is encompassed. The abstract ideas identified in the independent claims are the same as those identified as mathematic correlations, mathematic calculations, and mathematical relationships or as mental processes, concepts performed in the human mind including observations, evaluations, judgements and opinions, in MPEP 2106.04.
With respect to the argument that the claim is not directed to any abstract idea, because “it recites physical acts of performing the encoding assay which cannot be done in the human mind” This argument is not persuasive. The BRI of Claim 2, step (a), is the receipt of data. This was not considered, or determined to be abstract. It is noted, however, that the assay itself occurs outside the bounds of claim 1, and merely the results of the assay are received. No evidence is of record that this process produces materially differing nucleic acid sequence read data than prior art known processes, and this data receipt limitation can be met by receiving any sequence read data which comprises barcodes, tags, etc. Receipt of data is not a step carried out in the laboratory. Receipt of data is an Element in Addition (EIA) to the identified abstract ideas.
With respect to the argument that the claim is not directed to an abstract idea because “it aims to identify amino acid sequence of polypeptides present in a sample, which is not a mathematic concept, a method of organizing human activity, or a mental process” This argument is not persuasive. In the analysis of Claim 2, the remainder of the steps of claim 2 (steps b, c, d, and e) were identified as being directed to an abstract idea, and the particular category was identified for each. The Examiner pointed to support for this interpretation in the BRI, and in the specification.
With respect to the argument in the analysis under step 2A-2 that “examiners should explain why they [extra solution activity limitations] do not meaningfully limit the claim” and the assertion that the examiner failed to meet the requirements, this argument is unpersuasive. The examiner pointed out that these extra solution activities were carried out, outside the bounds of the claim, and thus could not provide integration into a practical application. The Examiner pointed out that the data gathering/ extra-solution activities did not meet any of the examples in MPEP 2106, and they still do not.
“Data gathering steps are not an abstract idea, they are extra-solution activity, as they collect the data needed to carry out the JE. The data gathering does not impose any meaningful limitation on the JE, or how the JE is performed. The additional limitation (data gathering) must have more than a nominal or insignificant relationship to the identified judicial exception. (MPEP 2106.04/.05, citing Intellectual Ventures LLC v. Symantec Corp, McRO, TLI communications, OIP Techs. Inc. v. Amason.com Inc., Electric Power Group LLC v. Alstrom S.A.).”
Merely receiving sequence read data as set forth in claim 2, is extra solution activity because it is a step that accepts data from a source. How the data is received does not affect any of the steps identified as the JE are carried out. Whether the data comes from a new experiment, or one saved in a database, steps (b-e) are carried out unchanged. How the data is received does not change any of the results of the JE processing steps. This is extra-solution activity, and Applicant is again directed to the analysis above, and MPEP 2106.04/ .05.
The examiner considered the claim as an ordered series of steps, and as a whole, and claim 2 remained patent-ineligible at step 2A-2. Receiving data, utilizing a general-purpose computer system, to carry out the abstract idea/ JE, remains insufficient to integrate that JE into a practical application.
With respect to the arguments asserting an improvement to technology, these arguments remain unpersuasive. The claims do not set forth the minimally sufficient set of steps required to achieve the improvement in the independent claim. To achieve the improvement, certain trained neural networks or trained machine learning models were required. Particular training information was required. The specification indicates that possibly two separate ML models are required, one to act on the raw encoder assay data, to deconvolve the extended recording tag, and a second to take the output of the first, and determine the most likely amino acid sequence. These elements are lacking in the independent claim.
Applicant’s asserted improvement comes from the analysis of the data, and not the data generation from the encoder assay. As claim 2 stands it still appears to claim the idea of the improvement, and not the actual improvement itself.
With respect to Applicant’s arguments regarding step 2B, and whether the examiner met the burden presented by Berkheimer, this argument is not persuasive. The examiner provided multiple prior art disclosures from more than a year before the effective filing date, to around the effective filing date, of prior art know procedures, including those acknowledged in the specification as being known in the prior art. The data generated by any of the identified prior art processes would be equivalent to that received in claim 2, absent evidence to the contrary. That meets the burden represented by Berkheimer, and the remainder of the 2B analysis.
“Activities such as data gathering do not improve the functioning of a computer, or comprise an improvement to any other technical field. The limitations do not require or set forth a particular machine, they do not effect a transformation of matter, nor do they provide an unconventional step (citing McRO and Trading Technologies Int’l v. IBG). Data gathering steps constitute a general link to a technological environment. Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception are insufficient to provide significantly more (as discussed in Alice Corp.,).”
The receipt of data does not improve the functioning of a computer. The receipt of data does not comprise an improvement to any other technical field. The receipt of the data does not require a particular machine. Receipt of data is not an unconventional step. Receipt of data, generated by an encoder assay, is a general link to the technological environment of high throughput polypeptide sequencing. The receipt of data was shown to be routine, well-understood and conventional, even in the art of high throughput polypeptide sequencing, and encoder assays. The receipt of the data does not present any unconventional process or data structure. This is insufficient to provide significantly more than the identified JE.
The alleged improvement is achieved by the elements identified as reciting an abstract idea.
According to the guidance set forth in MPEP 2106, this is an improvement to the judicial exception itself, and is not reflected back into a specific technological environment or practically applied process.
An improvement in the judicial exception itself is not an improvement in the technology. For example, in In re Board of Trustees of Leland Stanford Junior University, 989 F.3d 1367, 1370, 1373 (Fed. Cir. 2021) (Stanford I), Applicant argued that the claimed process was an improvement over prior processes because it ‘‘yields a greater number of haplotype phase predictions,’’ but the Court found it was not ‘‘an improved technological process’’ and instead was an improved ‘‘mathematical process.’’ The court explained that such claims were directed to an abstract idea because they describe ‘‘mathematically calculating alleles’ haplotype phase,’’ like the ‘‘mathematical algorithms for performing calculations’’ in prior cases. Notably, the Federal Circuit found that the claims did not reflect an improvement to a technological process, which would render the claims eligible (FR89 no.137, p58137, 7/17/2024).
Here, Applicant has provided an improved mathematical process of converting raw encoder assay data to binder identifier strings of data, which are then used in the improved mathematical process to provide a likely identity and sequence of one or more polypeptides in the sample.
The improvement in identification of a polypeptide sequence (carried out by the judicial exception) does not provide an improvement in the technology of receiving exogenous data. The collection of exogenous data is carried out, unchanged, whether or not the judicial exception is applied. (Cleveland Clinic Foundation: using well-known or standard laboratory techniques is not sufficient to show an improvement (MPEP2106.05(a)).
The improvement in identification of a polypeptide sequence (achieved by the judicial exception) does not require a non-conventional interaction with a specific element of a computer as was required in Enfish. The disputed claims in Enfish were patent-eligible because they were "directed to a specific improvement to the way computers operate, embodied in [a] self-referential table." Enfish, 822 F.3d at 1336. The court found that the "plain focus of the claims" there was on an improvement to computer functionality itself-a self-referential table for a computer database, designed to improve the way a computer carries out its basic functions of storing and retrieving data- not on a task for which a computer is used in its ordinary capacity. Id. at 1335-36. The court noted that the specification identified additional benefits conferred by the self-referential table (e.g., increased flexibility, faster search times, and smaller memory requirements), which further supported the court's conclusion that the claims were directed to an improvement of an existing technology. Id. at 1337 (citation omitted).
The improvement in identification of a polypeptide sequence (carried out by the judicial exception) does not improve the functionality of the computer itself as in Finjan, Visual Memory, or SRI Int’l. In Finjan, claims to virus scanning were found to be an improvement in computer technology. In Visual Memory, claims to an enhanced computer memory system were found to be directed to an improvement in computer capabilities. In SRI Int'l, claims to detecting suspicious activity by using network monitors and analyzing network packets were found to be an improvement in computer network technology.
The improvement in identification of a polypeptide sequence does not provide an improvement in computer animation or use rules to automate a subjective task of humans to create a sequence of synchronized, animated characters as in McRo. In McRO, it was not the mere presence of unconventional rules that led to patent eligibility. In McRO, "[t]he claimed improvement was to how the physical display operated (to produce better quality images)." SAP Am. v. InvestPic, LLC, 898 F.3d 1161, 1167 (Fed. Cir. 2018). The claims in McRO recited a step of applying the data sets generated using the specific claimed rules to a sequence of animated characters to produce lip synchronization and facial expression control of those animated characters. McRO, 837 F.3d at 1308. Thus, the claims were directed to an improvement in computer animation and used rules to automate a subjective task of humans to create a sequence of synchronized, animated characters. Id. at 1314--15.
In the claims at issue here, there is no such application of specifically claimed rules to produce an improved technological result. The process of identification of a polypeptide sequence using trained ML modeling is not a technological process; it is information evaluation.
Further, with respect to the arguments regarding the alleged improvement, it is unclear that the independent claims recite all the necessary and sufficient steps required to achieve that improvement. MPEP 2106.05(a): “An important consideration in determining whether a claim improves technology is the extent to which the claim covers a particular solution to a problem or a particular way to achieve a desired outcome, as opposed to merely claiming the idea of a solution or outcome. McRO, 837 F.3d at 1314-15, 120 USPQ2d at 1102- 03; DDR Holdings, 773F.3d at 1259, 113 USPQ2d at 1107.”
The MPEP sets forth that “if the examiner concludes the disclosed invention does not improve technology, the burden shifts to applicant to provide persuasive arguments supported by any necessary evidence to demonstrate that one of ordinary skill in the art would understand that the disclosed invention improves technology. Any such evidence submitted under 37 CFR 1.132 must establish what the specification would convey to one of ordinary skill in the art and cannot be used to supplement the specification.” Applicant’s arguments cannot take the place of evidence.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 2, 4, 12, 14, 16, 22, 28-30, 32, 34-35 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CHEE (WO2022/040098 A1, published 24 February 2022).
CHEE: WO 2022/040098, Sequential encoding methods and related kits, published 2/24/2022; which matured into National Stage Application US 2023/0136966 A1, published 4 May 2023. All paragraph references refer to the US PG-Pub).
The Effective Filing Date of this application is 11/9/2023. While there is a common assignee, there are no common inventors, and the publication date of the WO document is more than a year before the EFD of this application.
With respect to claims 2 and 30, CHEE teaches:
“2. (Currently amended) A method for identifying amino acid sequences of polypeptides of a plurality of polypeptides present in a sample, the method comprising:
(a) receiving, at one or more processors, a plurality of nucleic acid sequences generated by performing an encoding assay …”
Chee provides receiving nucleic acid sequence read data, which were generated by performing encoding assays for polypeptides or peptides present in sample (Fig 1), that comprise encoder barcodes, which correspond to binders at Figure 2, and Example 2 [0013, 0039, 0049-0051, 0056-0071, 0086, 0149-0159, 0198, 0352-0356 et al.] and sequencing the resulting polynucleotides. These are received by the computer system for analysis. Figure 1 is an illustration of the concept of the encoder assay, and Example 2 and its description provide the same steps for generating the data required.
Step 2(a)(i): [0011-0012] “FIG. 1B shows a cycle of encoding with the structure generated in FIG. 1A. The left panel of FIG. 1B shows a binding agent bound to the peptide, bringing a coding tag attached to the binding agent into proximity with the recording tag.”
Step 2(a)(ii): [0012-0013, 0064, 0066] “The middle panel of FIG. 1B shows the product of first two enzymatic reactions. Upon ligation of the 5′ end of the recording tag to the 3′ end of the coding tag, polymerase extends the 3′ (non-ligated) end of the recording tag to create a dsDNA molecule containing 2-base pair spacers adjacent to their respective type IIS RE sites. Following double stranding, the type IIS RE binds and cuts adjacent to its recognition site. The right panel of FIG. 1B illustrates the final product after all 3 enzymatic steps, where the dsDNA now contains the binding agent-specific barcode and a 2 nt 3′ overhang (OH) which serves as the spacer sequence.”
Step 2(a)(iii): [0011-0013, 0062] “The cycle of steps shown in FIG. 1Bmay be repeated one or more times with additional binding agents and coding tags to further extend the recording tag.”
Step 2(a)(iv): [0013, 0049-0051] “Fractions of encoded recording tags were evaluated by NGS sequencing and showed specific encoding results for both binding agents. Each error bar is constructed using 1 standard error from the mean.”
Chee defines the barcodes, coding tags, and spacers beginning at least at [0039] which meet the BRI of the barcodes [0039, 0044, 0082, 0092: sample identifying, or binder identifying, or 0087, 0174 location, or 0133 cycle-specific, 0172-0173 or partitioning] encoding tags [0007, 0012-0013, 0035, 0040, 0131-0146], recording tags [0017, 0042, 0064, 0067, 0076-0096 “extended recording tags” 0045-0046, 0057, 0150, 0194 et al.] and spacers [0041, 0060-0061, 0084-0085, 0138] of the claims. [0039-0046, 0096, 0145-0148, 0173, 0200, 0216, 0348, 0352].
Chee identifies prior art known processes for sequencing nucleic acids, such as the extended recording tags of the claims at [0047-0051, 0194-0210]. These steps inherently provide data equivalent to that which is to be received in claim 2.
With respect to claim 2 and “(b) converting, using the one or more processors, each nucleic acid sequence of the plurality of nucleic acid sequences into a binder identifier string…”
Chee provides in the analysis section beginning at least at [0193]: “[0210] Following sequencing of the nucleic acid libraries (e.g., of extended nucleic acids), the resulting sequences can be collapsed by their UMIs if used…”
“[0348] … methods for analyzing extended recording tags were disclosed in earlier published application US 2019/0145982 A1, US 2020/0348308 A1, US 2020/0348307 A1, US 2021/0208150 A1, WO 2020/223000, the contents of which are incorporated herein by reference in their entireties.”
With respect to Claim 2 and “(c) for each binder identifier string of the plurality of binder identifier strings, generating a plurality of peptidic reads for the binder identifier string…
(d) for each peptidic read of the plurality of peptidic reads, calculating a probability score …
(e) for each binder identifier string of the plurality of binder identifier strings, selecting one or more peptidic reads…
inferring amino acid sequences of polypeptides of the plurality of polypeptides present in the sample from the selected one or more peptidic reads.”
Chee provides deconvolving the identifier strings to identify what was bound, including [0103-0104, 0109-0110, 0150 (binding agent specific barcode deconvolving), 0210]:
“[0210] Following sequencing of the nucleic acid libraries (e.g., of extended nucleic acids), the resulting sequences can be collapsed by their UMIs if used and then associated to their corresponding polypeptides and aligned to the totality of the proteome. Resulting sequences can also be collapsed by their compartment tags and associated to their corresponding compartmental proteome, which in a particular embodiment contains only a single or a very limited number of protein molecules. Both protein identification and quantification can easily be derived from this digital peptide information.
“[0355] … The extended recording tags of the assay were subjected to PCR amplification and analyzed by next-generation sequencing (NGS), revealing barcode information about binding agents that were interacted with the macromolecules…. Fractions of encoded recording tags (percentage of extended recording tags to total amount of recording tags on the beads (extended and unextended)) were evaluated by NGS sequencing and showed specific encoding results for both binding agents.”
[0046]: “[0046] As used herein, the term “extended recording tag” refers to a recording tag to which information of at least one binding agent's coding tag (or its complementary sequence) has been transferred following binding of the binding agent to a polypeptide. Information of the coding tag may be transferred to the recording tag directly (e.g., ligation) or indirectly (e.g., primer extension). Information of a coding tag may be transferred to the recording tag enzymatically or chemically. An extended recording tag may comprise binding agent information of 1, … 200 or more coding tags. The base sequence of an extended recording tag may reflect the temporal and sequential order of binding of the binding agents identified by their coding tags, may reflect a partial sequential order of binding of the binding agents identified by the coding tags, or may not reflect any order of binding of the binding agents identified by the coding tags. In certain embodiments, the coding tag information present in the extended recording tag represents with at least 25%, … 99%, or 100% identity the polypeptide sequence being analyzed.”
[0058] “…The final extended recording tag associated with the macromolecule for analysis can comprise information from one or more coding tags. If multiple cycles are performed, the resulting extended recording tag then contains information built up from a series of binding events and multiple information transfer events from coding tags.”
[0194] “In some embodiments, the extended recording tag generated from performing the provided methods comprises information transferred from one or more coding tags. In some embodiments, the extended recording tags comprises a series of information transferred from a plurality of coding tags indicative of the order of binding by the binding agents.”
The BRI of the inference of the polypeptide sequence is met in CHEE by the terms “deconvolution” or “collapse” of the binder identifiers. [0039, 0046, 0194-0195, 0210] This deconvolution is computer-implemented, and each individual polynucleotide sequence read, comprising the set of barcodes that generated the binder identifier string, is analyzed. The binding profiles are the information as to whether a particular binder bound a target in a given round of the encoder assay. The calculated probabilities are disclosed in [0046].
[0039] “Barcodes can be used to computationally deconvolute the multiplexed sequencing data and identify sequence reads derived from an individual polypeptide, sample, library, etc. A barcode can also be used for deconvolution of a collection of polypeptides that have been distributed into small compartments for enhanced mapping. For example, rather than mapping a peptide back to the proteome, the peptide is mapped back to its originating protein molecule or protein complex.”
[0046] “ In certain embodiments, the coding tag information present in the extended recording tag represents with at least 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, or 100% identity the polypeptide sequence being analyzed.”
[0210] “Following sequencing of the nucleic acid libraries (e.g., of extended nucleic acids), the resulting sequences can be collapsed by their UMIs if used and then associated to their corresponding polypeptides and aligned to the totality of the proteome. Resulting sequences can also be collapsed by their compartment tags and associated to their corresponding compartmental proteome, which in a particular embodiment contains only a single or a very limited number of protein molecules. Both protein identification and quantification can easily be derived from this digital peptide information.”
Chee provides analysis of the binder identifier strings, by computer, throughout and [0210].
[0210] “Following sequencing of the nucleic acid libraries (e.g., of extended nucleic acids), the resulting sequences can be collapsed by their UMIs if used and then associated to their corresponding polypeptides and aligned to the totality of the proteome. Resulting sequences can also be collapsed by their compartment tags and associated to their corresponding compartmental proteome, which in a particular embodiment contains only a single or a very limited number of protein molecules. Both protein identification and quantification can easily be derived from this digital peptide information.
CHEE provides computer system implementation of the method of claim 2, meeting claim 30, throughout.
With respect to claim 4, the percentages are shown above.
With respect to claim 12, multiple barcode sequences can be used, falling within the 4-20 and [0148].
With respect to claims 14, CHEE teaches pluralities of polypeptides as required, throughout and in Examples 1 and 2.
With respect to claim 16, CHEE teaches how to determine binding profiles experimentally, in Examples 1 and 2.
With respect to claim 22, CHEE teaches binders which bind post-translational modifications in the sections on Binding Tags and Coding Tags, cited above.
With respect to claim 28, the sequence of all polypeptides in the sample can be analyzed, See Example 2, as well as the sections “macromolecule analysis assay”, “sample and macromolecule,” and “analysis” as cited above.
With respect to claim 29, any amount of polynucleotide sequences can be generated by next generation sequencing, as cited above.
With respect to claims 32, 34-35, NTAAs are defined and used at least at [0038, 0052, 0073, 0106-0120, 0125-0128, 0146, 0150-0151, 0185, 0189, 0190].
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipate