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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/10/2021 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Priority
Acknowledgment is made of applicant’s claim for priority. Application claims benefit of In Provisional Application No. 63/125297. As such, the effective filing date of claims 1-20 is 12/14/2020.
Claim Status
Claims 1-20 are pending.
Claims 1-20 are rejected.
Specification
The use of the term Nvidia GeForce, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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 are 1-20 rejected under 35 U.S.C. 101 because the claimed invention is directed to abstract ideas without significantly more. The claims recite a method of determining a molecular structure of a protein via the use of voxel data and neural networks to generate mappings and likelihoods of atomical placements. The judicial exception is not integrated into a practical application because while claims 1-20 attempt to integrate the exception into a practical application, said application is either generically recited computer elements that do not add a meaningful limitation to the abstract idea, or it is insignificant extra solution activity and simply implementing the abstract idea on a computer. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the computer elements only store and retrieve information in memory as well as perform basic calculations that are known to be well-understood, routine and conventional computer functions as recognized by the decisions listed in MPEP § 2106.05(d).
Framework with which to Analyze Subject Matter Eligibility:
Step 1: Are the claims directed to a category of statutory subject matter (a process, machine, manufacture, or composition of matter)? [see MPEP § 2106.03]
Claims are directed to statutory subject matter, specifically methods (claims 1-20).
Step 2A Prong One: Do the claims recite a judicially recognized exception, i.e., an abstract idea, a law of nature, or a natural phenomenon? [see MPEP § 2106.04(a)]
The claims herein recite abstract ideas, mental processes and mathematical concepts.
With respect to the Step 2A Prong One evaluation, the instant claims are found herein to recite abstract ideas that fall into the grouping of mental processes and mathematical concepts.
Claim 1: Determining a backbone structure based on the predicted likelihoods, amino acid sequences to the backbone structure based on the predicted likelihoods, determining locations of carbon, nitrogen, and oxygen atoms based on the likelihoods, and determining side-chain atoms based on the predicted structure are all processes of choosing, comparing, contrasting, and classifying which are all process which can be done with pen and paper or in the human mind and are therefore abstract ideas, specifically mental processes.
Claim 2: The function proposed is a verbal articulation of a mathematical process and thus an abstract idea, specifically a mathematical concept.
Claim 3: The function proposed is a verbal articulation of a mathematical process and thus an abstract idea, specifically a mathematical concept.
Claim 4: Maximizing the sum of all rewards to obtain an ideal alignment using a dynamic algorithm is a verbal articulation of a mathematical process and thus an abstract idea, specifically a mathematical concept.
Claim 5: The function proposed is a verbal articulation of a mathematical process and thus an abstract idea, specifically a mathematical concept.
Claim 6: A neural network configured to label each voxel with one or more likelihoods of atom types, a neural network configured to label each voxel with a likelihood that a backbone atom is associated with the voxel, a neural network configured to label each voxel with one or more likelihoods of secondary structures, a neural network configured to label each voxel with one or more likelihoods of amino acid types, are all processes of identifying and tagging information that can be done with pen and paper or in the human mind and are therefore abstract ideas, specifically mental processes.
Claim 7: Refining positions of the carbon and nitrogen atoms base on centers of mass of carbon atoms and nitrogen atoms, further refining the positions of carbon and nitrogen atoms based on molecular mechanics, and providing positions for oxygen atoms based on the positions of the carbon and nitrogen atoms are all processes of fine-tuning exact measurements that can be done with pen and paper or in the human mind and are therefore abstract ideas, specifically mental processes.
Claim 9: Rounding likelihoods is a verbal articulation of a mathematical process and thus an abstract idea, specifically a mathematical concept. Finding connected groups of voxels with a rounded value of one, and identifying disconnected areas of connected groups are processes of identifying patterns, comparing, and contrasting which are all process that can be done with pen and paper or in the human mind and are therefore abstract ideas, specifically mental processes.
Claim 10: Determining a point in space for each alpha atom of the disconnected chain is a process is a process of choosing, which can be done with pen and paper or in the human mind and is therefore an abstract idea, specifically a mental process. Conducting an optimization on the point cloud is a verbal articulation of a mathematical process and thus an abstract idea, specifically a mathematical concept.
Claim 11: Finding indices of all local maximums, and calculating a center of mass of all voxels within a specified distance are verbal articulations of mathematical processes and thus abstract ideas, specifically mathematical concepts.
Claim 12: Using a modified traveling salesman technique including scoring connections and considering Euclidean distance between atoms is a verbal articulation of a mathematical process and thus an abstract idea, specifically a mathematical concept.
Claim 13: Using one or more neural networks to predict one or more likelihoods, determining a backbone structure based on the predicted likelihoods, mapping amino acid sequences to the backbone structure based on the predicted likelihoods, determining locations of carbon, nitrogen, and oxygen atoms based on the likelihoods, and determining side-chain atoms based on the predicted structure are all are all processes of choosing, comparing, contrasting, and classifying which are all process which can be done with pen and paper or in the human mind and are therefore abstract ideas, specifically mental processes.
Claim 14: The function proposed is a verbal articulation of a mathematical process and thus an abstract idea, specifically a mathematical concept.
Claim 15: The function proposed is a verbal articulation of a mathematical process and thus an abstract idea, specifically a mathematical concept.
Claim 16: Maximizing the sum of all rewards to obtain an ideal alignment using a dynamic algorithm is a verbal articulation of a mathematical process and thus an abstract idea, specifically a mathematical concept.
Claim 17: The function proposed is a verbal articulation of a mathematical process and thus an abstract idea, specifically a mathematical concept.
Claim 18: Identifying two or more disconnected side chains of alpha atoms is a process of identifying patterns, and comparing and contrasting information, which are processes that can be performed with pen and paper or in the human mind and is thus an abstract idea, specifically a mental process.
Claim 19: Determining a point in space for each alpha atom of the disconnected chain is a process of choosing which can be done with pen and paper or in the human mind and is therefore an abstract idea, specifically a mental process. Conducting an optimization on the point cloud is a verbal articulation of a mathematical process and thus an abstract idea, specifically a mathematical concept.
Claim 20: Using one or more neural networks to predict one or more likelihoods, determining a backbone structure based on the predicted likelihoods, mapping amino acid sequences to the backbone structure based on the predicted likelihoods, determining locations of carbon, nitrogen, and oxygen atoms based on the likelihoods, and determining side-chain atoms based on the predicted structure are all are all processes of choosing, comparing, contrasting, and classifying which are all process which can be done with pen and paper or in the human mind and are therefore abstract ideas, specifically mental processes.
Step 2A Prong Two: If the claims recite a judicial exception under prong one, then is the judicial exception integrated into a practical application? [see MPEP § 2106.04(d) and MPEP §
2106.05(a)-(c) & (e)-(h)]
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 abstract ideas into a practical application.
The following claims recite the following additional elements in the form of non-abstract elements:
Claim 1: Using one or more neural networks to predict one or more likelihoods, is merely a use of a generically recited computer element (Example 47), to perform a mental task, specifically calculating likelihoods which are mathematical concepts. Receiving voxel data, and storing the molecular structure are both are insignificant extra solution activities specifically, mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)]. A computing system and non-transitory computer-readable medium are generic and nonspecific elements that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)].
Claim 6: Providing the voxel data to a plurality of neural networks is an insignificant extra solution activity specifically, mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)].
Claim 7: Providing initial positions for carbon and nitrogen atoms is an insignificant extra solution activity specifically, mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)].
Claim 13: Receiving voxel data, and storing the molecular structure are insignificant extra solution activities specifically, mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)]. A computing system, computer-executable instructions, processors and non-transitory computer-readable medium are generic and nonspecific elements that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)].
Claim 20: Receiving voxel data, and storing the molecular structure are insignificant extra solution activities specifically, mere data gathering (See Performing clinical tests on individuals to obtain input for an equation, In re Grams, 888 F.2d 835, 839-40; 12 USPQ2d 1824, 1827-28 (Fed. Cir. 1989) and Determining the level of a biomarker in blood, Mayo, 566 U.S. at 79, 101 USPQ2d at 1968. See also PerkinElmer, Inc. v. Intema Ltd., 496 Fed. App'x 65, 73, 105 USPQ2d 1960, 1966 (Fed. Cir. 2012) (assessing or measuring data derived from an ultrasound scan, to be used in a diagnosis)) [See MPEP § 2106.05(g)]. A computing system and non-transitory computer-readable medium are generic and nonspecific elements that do not improve the functioning of any computer or technology described herein [See MPEP § 2106.04(d)(1) and MPEP § 2106.05(d)].
Step 2B: If the claims do not integrate the judicial exception, do the claims provide an inventive concept? [see MPEP § 2106.05]
Because the additional claim elements do not integrate the abstract idea into a practical application, the claims are further examined under Step 2B, which evaluates whether the additional elements, individually and in combination, amount to significantly more than the judicial exception itself by providing an inventive concept.
The claims do not recite additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that are generic, conventional, nonspecific, or insignificant extra solution activity. These additional elements include:
The additional elements of receiving voxel data (Conventional: MPEP § 2106.05(d)(II)), providing the voxel data to a plurality of neural networks (Conventional: MPEP § 2106.05(d)(II)), providing initial positions for carbon and nitrogen atoms (Conventional: MPEP § 2106.05(d)(II)), and storing the molecular structure (Conventional: MPEP § 2106.05(d)(II)) are insignificant extra solution activities specifically, mere data gathering (See Receiving or transmitting data over a network, e.g., using the Internet to gather data, Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), TLI Communications LLC v. AV Auto. LLC, 823 F.3d 607, 610, 118 USPQ2d 1744, 1745 (Fed. Cir. 2016) (using a telephone for image transmission), OIP Techs., Inc., v. Amazon.com, Inc., 788 F.3d 1359, 1363, 115 USPQ2d 1090, 1093 (Fed. Cir. 2015) (sending messages over a network), 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), and Storing and retrieving information in memory, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015)) [See MPEP § 2106.05(g)]. Therefore, taken both individually and as a whole, the additional elements do not amount to significantly more than the judicial exception by providing an inventive concept.
The additional elements of a computing system, computer-executable instructions, processors, non-transitory computer-readable mediums, and using one or more neural networks to predict one or more likelihoods, are all generic and nonspecific elements of a computer that are well-understood, routine and conventional within the art and therefore do not improve the functioning of any computer or technology described therein (Receiving or transmitting data over a network, e.g., using the Internet to gather data, Symantec, 838 F.3d at 1321, 120 USPQ2d at 1362 (utilizing an intermediary computer to forward information), Performing repetitive calculations, Flook, 437 U.S. at 594, 198 USPQ2d at 199 (recomputing or readjusting alarm limit values), and Storing and retrieving information in memory, Versata Dev. Group, Inc. v. SAP Am., Inc., 793 F.3d 1306, 1334, 115 USPQ2d 1681, 1701 (Fed. Cir. 2015)) [See MPEP § 2106.05(d)(II)]. Therefore, taken both individually and as a whole, the additional elements do not amount to significantly more than the judicial exception by providing an inventive concept.
Therefore, claims 1-20, when the limitations are considered individually and as a whole, are rejected under 35 USC § 101 as being directed to non-statutory subject matter.
Novelty and Non-Obviousness
Claims 1-20 are free of the prior art. Specifically, while methods exist that implement maximum likelihood approaches to cryo-EM data, particularly within structure prediction (such as in the case of Scheres, Sjors H W. “RELION: implementation of a Bayesian approach to cryo-EM structure determination.” Journal of structural biology (2012) 519-30), these methods are directed to the alignment and use the prediction of voxels loosely in terms of merely predicting an image with multiple voxels, “This paper describes the implementation of the Bayesian approach to single-particle reconstruction” – page 520, column 1, paragraph 2, “a set of atomic coordinates of the 70S ribosome was converted to a density map of 128 x 128 x 128 voxels, with a voxel size of 2.8 Å, using the xmipp_convert_pdb2vol program…The resulting projections were then back-projected in their perfect orientations to generate a reconstructed density map, and the accuracy of this projection/reconstruction cycle was assessed by FSC-curves between this reconstruction and the original phantom…all particles were normalized, 115 particles were discarded after initial sorting, and the remaining 5053 particles were windowed to images of 128 x 128 pixels, with a pixel size of 2.12 Å” – page 523, column 1-2 under Experimental Procedures. Applicant proposes a wholly different approach in that each individual voxel is predicted as being one of several atoms, specifically limitations “predict one or more likelihoods for each voxel; determining, by the computing system, a backbone structure based on the predicted likelihoods; mapping, by the computing system, amino acid sequences to the backbone structure based on the predicted likelihoods, wherein mapping the amino acid sequences to the backbone structure based on the predicted likelihoods includes conducting an alignment technique that uses a reward function and a gap penalty; determining, by the computing system, locations of carbon, nitrogen, and oxygen atoms within the backbone structure based on the predicted likelihoods”, specifically in combination with each other. More recent papers such as Subramaniya et al. 2019 (Maddhuri Venkata Subramaniya, Sai Raghavendra et al. “Protein secondary structure detection in intermediate-resolution cryo-EM maps using deep learning.” Nature methods (2019) 911-917), use deep learning and cryo-EM data to predict structure from voxels, however said voxels represent density values of secondary structures such as alpha helixes and beta sheets, “The voxel reads the density values, which are processed through the deep CNN, and outputs a detected secondary structure (that is, α-helices, β-sheets and what we term ‘other structures’) for the structure at the center of the voxel” – page 911, column 2, paragraph 2. Finally, papers such as Aramov et al. (Avramov, Todor Kirilov et al. “Deep Learning for Validating and Estimating Resolution of Cryo-Electron Microscopy Density Maps †.” Molecules (Basel, Switzerland) (2019) 1-19) and Zhon et al. (Zhong, Ellen D., et al. "Reconstructing continuous distributions of 3D protein structure from cryo-EM images." arXiv preprint (2019) 1-20) use voxel wise classification but only to produce density maps, not to classify atomic type. Additionally, the use of multiple neural networks each working in concert to predict specific elements associated with each atom (it’s type, whether it is a backbone atom, whether it has a secondary structure attached, and what amino acid is associated with it) also seems to be free of the prior art. While issues remain as pertains to sections 35 USC § 101, the current invention is free of the prior art.
Conclusion
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/K.N.A./ Examiner, Art Unit 1687
/OLIVIA M. WISE/ Supervisory Patent Examiner, Art Unit 1685