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 .
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 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.
Claim Status
Claims 1-18 and 28-29 are pending.
Claims 19-27 and 30-40 are canceled.
Claims 1-18 and 28-29 are under examination.
Claims 1-18 and 28-29 are rejected.
Priority
This application is a 371 of PCT/EP2021/082684 11/23/2021 which claims benefit of 63/118,917 11/28/2020 and claims benefit of 63/187,362 05/11/2021.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 11/13/2023 and 02/06/2026 are in compliance with the provisions of 37 CFR 1.97 and have therefore been considered. Signed copies of the IDS documents are included with this Office Action.
Drawings
The Drawings submitted 03/15/2023 are accepted.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-18 and 28-29 are rejected under 35 U.S.C. 101 because the claimed invention is directed to one or more judicial exceptions without significantly more.
MPEP 2106 organizes judicial exception analysis into Steps 1, 2A (Prongs One and Two) and 2B as follows below. MPEP 2106 and the following USPTO website provide further explanation and case law citations: uspto.gov/patent/laws-and-regulations/examination-policy/examination-guidance-and-training-materials.
Framework with which to Evaluate Subject Matter Eligibility:
Step 1: Are the claims directed to a process, machine, manufacture, or composition of matter;
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;
Step 2A, Prong Two: If the claims recite a judicial exception under Prong One, then is the judicial exception integrated into a practical application (Prong Two); and
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept.
Framework Analysis as Pertains to the Instant Claims:
Step 1
With respect to Step 1: yes, the claims are directed to method, system, and storage media, i.e., a process, machine, or manufacture within the above 101 categories [Step 1: YES; See MPEP § 2106.03].
Step 2A, Prong One
With respect to Step 2A, Prong One, the claims recite judicial exceptions in the form of abstract ideas. The MPEP at 2106.04(a)(2) further explains that abstract ideas are defined as:
mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations);
certain methods of organizing human activity (fundamental economic practices or principles, managing personal behavior or relationships or interactions between people); and/or
mental processes (procedures for observing, evaluating, analyzing/ judging and organizing information).
With respect to the instant claims, under the Step 2A, Prong One evaluation, the claims are found to recite abstract ideas that fall into the grouping of mental processes (in particular procedures for observing, analyzing and organizing information) and mathematical concepts (in particular mathematical relationships and formulas) are as follows:
Independent claims 1 and 28-29:
processing an input comprising the initial MSA representation and the initial pair embeddings using an embedding neural network to generate an output that comprises a final MSA representation and a respective final pair embedding for each pair of amino acids in the protein, wherein the embedding neural network comprises a sequence of update blocks, wherein each update block has a respective set of update block parameters and performs operations comprising:
updating the current MSA representation, in accordance with values of the update block parameters of the update block, based on the current pair embeddings; and
updating the current pair embeddings, in accordance with the values of the update block parameters of the update block, based on the updated MSA representation; and
determining a predicted structure of the protein using the final MSA representation, the final pair embeddings, or both.
Dependent claim 2:
updating the current MSA representation using attention over the embeddings in the MSA representation, wherein the attention is conditioned on the current pair embeddings.
Dependent claim 3:
generating, based on the current MSA representation, a plurality of attention weights;
generating, based on the current pair embeddings, a respective attention bias corresponding to each of the attention weights;
generating a plurality of biased attention weights based on the attention weights and the attention biases; and
updating the embeddings in the current MSA representation using attention over the embeddings in the current MSA representation based on the biased attention weights.
Dependent claim 5:
applying a transformation operation to the updated MSA representation; and
updating the current pair embeddings by adding a result of transformation operation to the current pair embeddings.
Dependent claim 7:
updating the current pair embeddings using attention over the current pair embeddings, wherein the attention is conditioned on the current pair embeddings.
Dependent claim 8:
generating, based on the current pair embeddings, a plurality of attention weights;
generating, based on the current pair embeddings, a respective attention bias corresponding to each attention weight;
generating a plurality of biased attention weights based on the attention weights and the attention biases; and
updating the current pair embeddings using attention over the current pair embeddings based on the biased attention weights.
Dependent claim 10:
updating the current pair embedding, based on the biased attention weights, using attention over only current pair embeddings that are located in a same column as the current pair embedding in an arrangement of the current pair embeddings into a two-dimensional array.
Dependent claim 11:
assembling the representations of the MSAs corresponding to the chains into a block diagonal array.
Dependent claim 12:
processing an input comprising the final pair embeddings using a folding neural network to generate an output that defines the predicted structure of the protein, comprising, for each of a plurality of pairs of amino acids in the protein:
processing a final pair embedding for the pair of amino acids, in accordance with values of folding neural network parameters, to generate an output specifying a probability distribution over a set of possible distances between the pair of amino acids in a structure of the protein.
Dependent claim 13:
processing an input comprising the final pair embeddings using a folding neural network to generate an output that defines the predicted structure of the protein, comprising:
obtaining an initial single embedding and initial values of structure parameters for each amino acid in the protein, wherein the structure parameters for each amino acid comprise location parameters that specify a predicted three-dimensional spatial location of the amino acid in the structure of the protein;
processing a folding network input comprising the final pair embeddings, the initial embedding for each amino acid in the protein, and the initial values of the structure parameters for each amino acid in the protein using the folding neural network to generate a network output comprising final values of the structure parameters for each amino acid in the protein, wherein the folding neural network comprises a plurality of update blocks, wherein each update block comprises a plurality of neural network layers and is configured to:
receive an update block input comprising the final pair embeddings, a current single embedding for each amino acid in the protein, and current values of the structure parameters for each amino acid in the protein; and
process the update block input to update the current single embedding and the current values of the structure parameters for each amino acid in the protein; wherein the final values of the structure parameters for each amino acid in the amino acid sequence collectively characterize the predicted structure of the protein.
Dependent claim 14:
determining the initial single embedding for each amino acid in the protein based on the final MSA representation
Dependent claim 17:
updating the current single embedding for each amino acid in the protein; and
updating the current values of the structure parameters for each amino acid in the protein based on the updated single embeddings for the amino acids in the protein.
Dependent claim 18:
generate an output that defines a predicted three-dimensional spatial location of each atom in each amino acid in the protein.
Dependent claims 4, 6, 9, and 15-16 recite further steps that limit the judicial exceptions in independent claims 3, 5, 8, 13, and 15 and, as such, also are directed to those abstract ideas. For example, claim 4 further limits the embedding of the MSA representation of claim 3, claim 6 further limits the transformation operation of claim 5, claim 9 further limits the current pair embeddings of claim 8, claim 15 further limits the structure parameter of claim 13 and claim 16 further limits the rotation parameters of claim 15;
Therefore, claims 1, 28-29 and those claims dependent therefrom recite an abstract idea [Step 2A, Prong 1: YES; See MPEP § 2106.04].
Step 2A, Prong Two
Under the BRI, the instant claims recite judicial exceptions that are an abstract idea of the type that is in the grouping of a “mental process”, such as procedures for evaluating, analyzing or organizing information, and forming judgement or an opinion. The instant claims further recite judicial exceptions that are an abstract idea of the type that is in the grouping of a “mathematical concept”, such as mathematical relationships and mathematical equations.
The claim recites determining. The human mind is capable of determining a predicted structure of the protein using the final MSA representation, the final pair embeddings, or both.
The claims recite a mathematical concepts of processing an input … using an embedding neural network, updating the current MSA representation, updating the current pair embeddings, determining a predicted structure of the protein, updating the current MSA representation using attention over the embeddings, generating, based on the current MSA representation, a plurality of attention weights, generating, based on the current pair embeddings, a respective attention bias corresponding to each of the attention weights, generating a plurality of biased attention weights based on the attention weights and the attention biases, updating the embeddings in the current MSA representation using attention over the embeddings, applying a transformation operation, updating the current pair embeddings by adding a result of transformation operation to the current pair embeddings, updating the current pair embeddings using attention over the current pair embeddings, wherein the attention is conditioned on the current pair embeddings, generating, …, a plurality of attention weights, generating, …, a respective attention bias corresponding to each attention weight, generating a plurality of biased attention weights, updating the current pair embeddings using attention over the current pair embeddings, updating the current pair embedding, assembling the representations of the MSAs, processing an input… using a folding neural network, processing a final pair embedding, obtaining an initial single embedding and initial values, processing a folding network input, receive an update block input , process the update block input, determining the initial single embedding, updating the current single embedding, updating the current values, generate an output.
Because the claims do recite judicial exceptions, direction under Step 2A, Prong Two, provides that the claims must be examined further to determine whether they integrate the judicial exceptions into a practical application (MPEP 2106.04(d)). A claim can be said to integrate a judicial exception into a practical application when it applies, relies on, or uses the judicial exception in a manner that imposes a meaningful limit on the judicial exception. This is performed by analyzing the additional elements of the claim to determine if the judicial exceptions are integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exceptions, the claim is said to fail to integrate the judicial exceptions into a practical application (MPEP 2106.04(d).III).
Additional elements, Step 2A, Prong Two
With respect to the instant recitations, the claims recite the following additional elements:
Independent claims, 1 and 28-29:
obtaining an initial multiple sequence alignment (MSA) representation that represents a respective MSA corresponding to each chain in the protein; obtaining a respective initial pair embedding for each pair of amino acids in the protein
Dependent claim 11:
obtaining a respective representation of the MSA corresponding to each chain in the protein as a two-dimensional array of embeddings
The claims also include non-abstract computing elements. For example, independent claims 1 and 28-29 include a data processing apparatus, a system, and non-transitory computer storage media.
Considerations under Step 2A, Prong Two
With respect to Step 2A, Prong Two, the additional elements of the claims do not integrate the judicial exceptions into a practical application for the following reasons. Those steps directed to data gathering, such as “obtaining”, perform functions of collecting the data needed to carry out the judicial exceptions. Data gathering and outputting do not impose any meaningful limitation on the judicial exceptions, or on how the judicial exceptions are performed. Data gathering and outputting steps are not sufficient to integrate judicial exceptions into a practical application (MPEP 2106.05(g)).
Further steps directed to additional non-abstract elements of “a data processing apparatus, a system, and non-transitory computer storage media” do not describe any specific computational steps by which the “computer parts” perform or carry out the judicial exceptions, nor do they provide any details of how specific structures of the computer, such as the computer-readable recording media, are used to implement these functions. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, and therefore the claim does not integrate that judicial exceptions into a practical application. The courts have weighed in and consistently maintained that when, for example, a memory, display, processor, machine, etc.… are recited so generically (i.e., no details are provided) that they represent no more than mere instructions to apply the judicial exception on a computer, and these limitations may be viewed as nothing more than generally linking the use of the judicial exception to the technological environment of a computer (MPEP 2106.05(f)).
Thus, none of the claims recite additional elements which would integrate a judicial exception into a practical application, and the claims are directed to one or more judicial exceptions [Step 2A, Prong 2: NO; See MPEP § 2106.04(d)].
Step 2B (MPEP 2106.05.A i-vi)
According to analysis so far, the additional elements described above do not provide significantly more than the judicial exception. A determination of whether additional elements provide significantly more also rests on whether the additional elements or a combination of elements represents other than what is well-understood, routine, and conventional. Conventionality is a question of fact and may be evidenced as: a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to the instant claims, the courts have found that receiving and outputting data are well-understood, routine, and conventional functions of a computer when claimed in a merely generic manner or as insignificant extra-solution activity (see Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), buySAFE, Inc. v. Google, Inc., 765 F.3d 1350, 1355, 112 USPQ2d 1093, 1096 (Fed. Cir. 2014) (computer receives and sends information over a network), Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015), and OIP Techs., 788 F.3d at 1363, 115 USPQ2d at 1092-93, as discussed in MPEP 2106.05(d)(II)(i)).
As such, the claims simply append well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception (MPEP2106.05(d)). The data gathering steps as recited in the instant claims constitute a general link to a technological environment which is insufficient to constitute an inventive concept which would render the claims significantly more than the judicial exception (MPEP2106.05(g)&(h)).
With respect to claims 1 and 28-29 and those claims dependent therefrom, the computer-related elements or the general purpose computer do not rise to the level of significantly more than the judicial exception. The claims state nothing more than a generic computer which performs the functions that constitute the judicial exceptions. Hence, these are mere instructions to apply the judicial exceptions using a computer, which the courts have found to not provide significantly more when recited in a claim with a judicial exception (see MPEP 2106.06(A)). The specification also notes that computer processors and systems, as example, are commercially available or widely used at [208-209]. The additional elements are set forth at such a high level of generality that they can be met by a general purpose computer. Therefore, the computer components constitute no more than a general link to a technological environment, which is insufficient to constitute an inventive concept that would render the claims significantly more than the judicial exceptions (see MPEP 2106.05(b)I-III).
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself [Step 2B: NO; See MPEP § 2106.05].
Therefore, the instant claims are not drawn to eligible subject matter as they are directed to one or more judicial exceptions without significantly more. For additional guidance, applicant is directed generally to the MPEP § 2106.
Claim Rejections - 35 USC § 102
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) 1 and 28-29 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Jumper et al. (Jumper, John, et al. "AlphaFold 2." Fourteenth Critical Assessment of Techniques for Protein Structure Prediction 13 (2020), newly cited).
Regarding claims 1 and 28-29 Jumper discloses the recited "method performed by one or more data processing apparatus" Visualizations: The PyMOL Molecular Graphics System, Version 2.0. PyMol requires an operating system of a general-purpose computer such as Windows, Mac, or LINUX. These general-purpose computers require the recited “a system comprising: one or more computers; and one or more storage devices communicatively coupled to the one or more computers" (preamble of claim 28) and "one or more non-transitory computer storage media storing instructions that when executed by the one or more computers…" (preamble of claim 29).
Claims 1 and 28-29 are directed to a method performed by one or more data processing apparatus for predicting a structure of a protein comprising one or more chains, wherein each chain comprises a sequence of amino acids, the method comprising: obtaining an initial multiple sequence alignment (MSA) representation that represents a respective MSA corresponding to each chain in the protein; obtaining a respective initial pair embedding for each pair of amino acids in the protein; processing an input comprising the initial MSA representation and the initial pair embeddings using an embedding neural network to generate an output that comprises a final MSA representation and a respective final pair embedding for each pair of amino acids in the protein, wherein the embedding neural network comprises a sequence of update blocks, wherein each update block has a respective set of update block parameters and performs operations comprising: receiving a current MSA representation and a respective current pair embedding for each pair of amino acids in the protein; updating the current MSA representation, in accordance with values of the update block parameters of the update block, based on the current pair embeddings; and updating the current pair embeddings, in accordance with the values of the update block parameters of the update block, based on the updated MSA representation; and determining a predicted structure of the protein using the final MSA representation, the final pair embeddings, or both.
Jumper discloses Alphafold 2 [title]. Jumper further discloses predicting a structure of a protein comprising one or more chains, wherein each chain comprises a sequence of amino acids, by obtaining an initial multiple sequence alignment (MSA) representation and obtaining a respective initial pair embedding for each pair of amino acids; processing an input comprising the initial MSA representation and the initial pair embeddings using an neural network that generates an output that comprises a MSA representation and a pair embedding , wherein the embedding neural network comprises a sequence of update blocks: receiving a current MSA representation and a respective current pair embedding; updating the current MSA representation; and updating the current pair embeddings, based on the updated MSA representation; and determining a predicted structure of the protein using the final MSA representation, the final pair embeddings, or both [p. 10].
Claim 2 is directed to the method of claim 1, wherein the current MSA representation comprises a plurality of embeddings, and wherein updating the current MSA representation based on the current pair embeddings comprises: updating the current MSA representation using attention over the embeddings in the MSA representation, wherein the attention is conditioned on the current pair embeddings.
Jumper discloses updating the current MSA representation using attention over the embeddings in the MSA representation, wherein the attention is conditioned on the current pair embeddings [p. 10].
Conclusion
No claims are allowed.
It is noted that claims 3-18 are free from the prior because the prior art does not teach nor fairly suggest the details of the update blocks or structure model. The closest prior art is Jumper. Jumper teaches predicting a structure of a protein comprising one or more chains, wherein each chain comprises a sequence of amino acids, by obtaining an initial multiple sequence alignment (MSA) representation and obtaining a respective initial pair embedding for each pair of amino acids; processing an input comprising the initial MSA representation and the initial pair embeddings using an neural network that generates an output that comprises a MSA representation and a pair embedding , wherein the embedding neural network comprises a sequence of update blocks: receiving a current MSA representation and a respective current pair embedding; updating the current MSA representation; and updating the current pair embeddings, based on the updated MSA representation; and determining a predicted structure of the protein using the final MSA representation, the final pair embeddings, or both [p. 10]. However, Jumper is silent to specific details of the model.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Dawn M. Bickham whose telephone number is (703)756-1817. The examiner can normally be reached M-Th 7:30 - 4:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Olivia Wise can be reached at 571-272-2249. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/D.M.B./Examiner, Art Unit 1685
/Soren Harward/Primary Examiner, TC 1600
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