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 .
DETAILED ACTION
Status of Claims
The present Office Action is pursuant to Applicant’s communication on 02-24-2023; current application filed on 02-24-2023. This application is a CON of PCT/US2021/048009 08/27/2021 PCT/US2021/048009 has PRO 63/071,490 08/28/2020.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 02-24-2023, have been acknowledged. The submissions are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 1-15 is/are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Step 1
Claim(s) 1-15 is/are within the four statutory categories. Claim(s) 1-15 is/are drawn to a method1, non-transitory computer-readable2 which means that said claims(s) is/are within the four statutory categories (i.e. process). However, as will be shown below, arguendo, Aforementioned claim(s) is/are nonetheless unpatentable under 35 U.S.C. 101.
Prong 1 of Step 2A
Claim(s) 1, which is/are representative of the inventive concept, recite(s):
1. A method comprising:
receiving, by a processor, input that specifies
(i) an amino acid sequence that includes a wildcard character that is representative of a wildcard amino acid,
wherein the wildcard amino acid represents any known amino acid, and
(ii) a target molecule;
identifying, by the processor, a computational workflow based on the target molecule;
providing, by the processor, the amino acid sequence to the computational workflow as input,
wherein the computational workflow is configured to produce a series of metrics as output, and
wherein each metric is indicative of a simulated interaction between the target molecule and a variation of the amino acid sequence in which the wildcard amino acid is replaced with a different amino acid; and
causing, by the processor, display of analysis of the series of metrics on an interface.
The underlined limitations as shown above, given the broadest reasonable interpretation, cover the abstract ideas of a mental process and/or a certain method of organizing human activity because they recite a process that could be practically performed in the human mind (i.e. observations, evaluations, judgments, and/or opinions – in this case the highlighted claim limitation(s) directed to an abstract idea (simulating a biological process via mathematical modeling), the claims akin to simulating how a plane flies by testing every possible wing shape in a digital tunnel, but wherein the claims have not invented a new wing or a better engine, rather automating mathematics of flight – the claims simulating how proteins “fly” (fold/bind), wildcards corresponding to requests to try every shape, without the claims changing how a computer works – only what data the computer is crunching – a “mental process” performed faster by a computer/machine, the use of a modular workflow to organize software akin to building a library with efficient rolling carts, the idea of putting books of a library in order, or using a modular cart system to move the books just the use of standard tools corresponding to the carts, this moving of carts, including in a predetermined order or not being an organization of human activity or data management, not specifically solving a specific bottleneck in computer architecture, the claims not detailing a practical a practical application showing a physical transformation (such as altering a chemical compound3, administering a specific drug to a patient, or improving the physical functioning of the computer itself), in other words, information itself, without a practical, physical application woven into the claims, is abstract, or in other words, the claims are akin to using a pen and paper, but for the recitation of generic computer components (i.e. the computer), e.g. see MPEP 2106.04(a)(2). Any limitations not identified above as part of the abstract ideas are deemed “additional elements,” and will be discussed in further detail below.
Dependent claim(s) 2-8, 10-11 and 13-15, include other limitations, for example:
2. The method of claim 1, wherein the computational workflow is comprised of multiple software modules that are arranged in a predetermined order.
3. The method of claim 2, wherein each software module is independently manipulable and executable by the processor.
4. The method of claim 1, wherein the computational workflow is further configured to predict a series of structural formations, each of which is associated with a corresponding variation of the amino acid sequence, that are computationally docked against the target molecule.
5. The method of claim 1, wherein the input further specifies that the amino acid sequence is not to interact with the target molecule.
6. The method of claim 1, wherein the wildcard character is one of multiple wildcard characters included in the amino acid sequence.
7. The method of claim 6, wherein a total number of variations of the amino acid sequence for which metrics are produced is 22n, where n is the number of wildcard characters in the amino acid sequence.
8. The method of claim 1,
wherein the amino acid sequence is one of multiple amino acid sequences specified in the input, and wherein each amino acid sequence of the multiple amino acid sequences is separately provided to the computational workflow so as to independently simulate the interaction of amino acid sequences with wildcard amino acids in different locations.
10. The non-transitory medium of claim 9, wherein the database is a graph database.
11. The non-transitory medium of claim 9, wherein the description is format-ted in accordance with the simplified molecular-input line-entry system (SMILES) format, SMILES arbitrary target specification (SMARTS) format, or International Chemical Identifier (InChI) format.
13. The method of claim 12, further comprising:
generating, by the processor, variations of the chemical or biological structure by selectively mutating an amino acid; and
obtaining, by the processor, structural formations for the variations of the chemical or biological structure,
wherein each structural formation is associated with a corresponding variation of the chemical or biological structure.
14. The method of claim 13, wherein the simulation involves computationally simulating interactions in the target environment using the structural formations to identify native biological structures, if any, that are likely to affect activity of the chemical or biological structure when introduced to the target environment.
15. The method of claim 12, wherein the simulation measures folding and/or docking capabilities of the chemical or biological structure in the target environ-ment, and wherein the computational workflow produces, as output, a first metric in accordance with a protein folding benchmark and/or a second metric in ac-cordance with a molecular interaction benchmark.
However these dependent claims only serve to further narrow the abstract idea, and a claim may not preempt abstract ideas, even if the judicial exception is narrow, e.g. see MPEP 2106.04. Additionally, any limitations in dependent claim(s) 2-8, 10-11 and 13-15 are deemed additional elements to the abstract idea, and will be further addressed below. Hence dependent claim(s) 2-8, 10-11 and 13-15 are nonetheless directed towards fundamentally the same abstract idea as independent Claim(s) 1, 9, 12.
Prong 2 of Step 2A
Claim(s) 1, 9, 12 is/are not integrated into a practical application because the additional elements (i.e. comprising non-underlined limitations above – in this case a processor of an electronic device, non-transitory computer-readable medium)
amount to no more than limitations which:
amount to mere instructions to apply an exception – for example, the recitation of a computer, which amounts to merely invoking a computer as a tool to perform the abstract idea, e.g. see ¶¶1-105 of the present Specification, see MPEP 2106.05(f);
generally link the abstract idea to a particular technological environment or field of use, which amounts to limiting the abstract idea to the field of healthcare, see MPEP 2106.05(h); and/or
add insignificant extra-solution activity to the abstract idea, see MPEP 2106.05(g).
Additionally, dependent claim(s) 2-8, 10-11 and 13-15 include other limitations, but these limitations also amount to no more than generally linking the abstract idea to a particular technological environment or field of use, and/or do not include any additional elements beyond those already recited in independent Claim(s) 1, 9, 12, hence also do not integrate the aforementioned abstract idea into a practical application.
Step 2B
Claim(s) 1, 9, 12 do/does not include additional elements that are sufficient to amount to “significantly more” than the judicial exception because the additional elements (i.e. comprising non-underlined limitations above – in this case a processor of an electronic device, non-transitory computer-readable medium), as stated above, are directed towards no more than limitations that amount to mere instructions to apply the exception, generally link the abstract idea to a particular technological environment or field of use, and/or add insignificant extra-solution activity to the abstract idea, wherein the insignificant extra-solution activity comprises limitations which:
amount to elements that have been recognized as well-understood, routine, and conventional activity in particular fields, as demonstrated by:
The Specification expressly disclosing that the additional elements are well-understood, routine, and conventional in nature:
¶¶1-105 of the Specification discloses that the additional elements (i.e. the computer) comprise a plurality of different types of generic computing systems that are configured to perform generic computer functions (i.e. receive and process data) that are well-understood, routine, and conventional activities previously known to the pertinent industry (i.e. healthcare);
Relevant court decisions: The following are examples of court decisions demonstrating well-understood, routine and conventional activities, e.g. see MPEP 2106.05(d)(II):
Storing and retrieving information in memory, e.g. see Versata Dev. Group, Inc. v. SAP Am., Inc. – similarly, the current invention recites storing or uploading media;
Dependent claim(s) 2-8, 10-11 and 13-15 include other limitations, but none of these limitations are deemed significantly more than the abstract idea because, as stated above, the limitations of the aforementioned dependent claims amount to no more than generally linking the abstract idea to a particular technological environment or field of use, and/or do not recite any additional elements not already recited in independent claim(s) 1, 9, 12 hence does not amount to “significantly more” than the abstract idea.
Thus, taken alone, the additional elements do not amount to significantly more than the abstract idea identified above. Furthermore, looking at the limitations as an ordered combination adds nothing that is not already present when looking at the elements taken individually, and there is no indication that the combination of elements improves the functioning of a computer or improves any other technology, and their collective functions merely provide conventional computer implementation.
Therefore, whether taken individually or as an ordered combination, claim(s) 1-15 is/are nonetheless rejected under 35 U.S.C. 101 as being directed to non-statutory subject matter.
Claim Rejections - 35 USC § 103
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.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-10 and 12-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zanghellini4 in view of Ramnarayan5.
Regarding claim(s) 1, 9, 12, Zanghellini discloses: A method, A non-transitory medium with instructions stored thereon that, when executed by a processor of an electronic device, cause the electronic device to perform operations comprising comprising:
receiving, by a processor, input that specifies6
an amino acid sequence that includes a wildcard character that is representative of a wildcard amino acid, wherein the wildcard amino acid represents any known amino acid, and (ii) a target molecule; [“computational redesign of the wild-type amino-acid sequence is carried out, preferably through one or more iterations between computational docking and computational redesign, to obtain new sequences predicted to have the desired function”7]
identifying, by the processor, a computational workflow based on the target molecule8; [“computational redesign of the wild-type amino-acid sequence is carried out, preferably through one or more iterations between computational docking and computational redesign, to obtain new sequences predicted to have the desired function”9]
providing, by the processor, the amino acid sequence to the computational workflow as input, wherein the computational workflow is configured to produce a series of metrics as output, [“selecting a suitable amino acid sequence comprises scoring the amino acid sequences by computationally docking the ligand, and optimizing the positioning of the amino acid side chain and main chain atoms by minimizing the energy of the ligand(s)/transition state(s )-structure interaction, the protein structure energy and/or by minimizing the free energy of ligand(s)/transition state(s )”10] and
Regarding [d]-[e], Zanghellini does not explicitly disclose as disclosed by Ramnarayanb:
wherein each metric is indicative of a simulated interaction between the target molecule and a variation of the amino acid sequence in which the wildcard amino acid is replaced with a different amino acid11; [“The method of claim 1, wherein the binding interactions are determined by: calculating the free energy of binding between the protein structural variant and the docked drug molecule”12] and
causing, by the processor, display of analysis of the series of metrics on an interface. [“The database interface also provides access to other databases, such as databases of chemical structures and public domain databases such as GenBank and the Protein Data Bank. The OpenGL and C++ module has real-time interaction with the sequence display and sequence analysis modules, such that highlighting residues in one display results in highlighting those same residues in other displays”13]
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to have modified Zanghellini, including mechanism(s) [d]-[e] as taught by Ramnarayan. One of ordinary skill would have been so motivated to employ said mechanism(s) allowing for simulation of different amino acid replacements.
Regarding claim(s) 2, Zanghellini-Ramnarayan as a combination discloses: The method of claim 1, Zanghellini disclosing: wherein the computational workflow is comprised of multiple software modules that are arranged in a predetermined order. [Employing steps in an operation flow14]
Regarding claim(s) 3, Zanghellini-Ramnarayan as a combination discloses: The method of claim 2, Zanghellini disclosing: wherein each software module is independently manipulable and executable by the processor. [Employing steps in an operation flow either employing a manual operator or an automated choice software flow15]
Regarding claim(s) 4, Zanghellini-Ramnarayan as a combination discloses: The method of claim 1, Zanghellini disclosing: wherein the computational workflow is further configured to predict a series of structural formations, each of which is associated with a corresponding variation of the amino acid sequence, that are computationally docked against the target molecule. [“computational redesign of the wild-type amino-acid sequence is carried out, preferably through one or more iterations between computational docking and computational redesign, to obtain new sequences predicted to have the desired function”16]
Regarding claim(s) 5, Zanghellini-Ramnarayan as a combination discloses: The method of claim 1, Zanghellini disclosing: wherein the input further specifies that the amino acid sequence is not to interact with the target molecule (i.e., sequence redesign and energy calculation). [“computational redesign of the wild-type amino-acid sequence is carried out, preferably through one or more iterations between computational docking and computational redesign, to obtain new sequences predicted to have the desired function”17]
Regarding claim(s) 6, Zanghellini-Ramnarayan as a combination discloses: The method of claim 1, Zanghellini disclosing: wherein the wildcard character is one of multiple wildcard characters included in the amino acid sequence. [“computational redesign of the wild-type amino-acid sequence is carried out, preferably through one or more iterations between computational docking and computational redesign, to obtain new sequences predicted to have the desired function”18]
Regarding claim(s) 7, Zanghellini-Ramnarayan as a combination discloses: The method of claim 6, Zanghellini disclosing: wherein a total number of variations of the amino acid sequence for which metrics are produced is 22n, where n is the number of wildcard characters in the amino acid sequence. [Employing E. Coli in association with optionally designed proteins19]
Regarding claim(s) 8, Zanghellini-Ramnarayan as a combination discloses: The method of claim 1, Zanghellini disclosing: wherein the amino acid sequence is one of multiple amino acid sequences specified in the input, and wherein each amino acid sequence of the multiple amino acid sequences is separately provided to the computational workflow so as to independently simulate the interaction of amino acid sequences with wildcard amino acids in different locations. [“computational redesign of the wild-type amino-acid sequence is carried out, preferably through one or more iterations between computational docking and computational redesign, to obtain new sequences predicted to have the desired function”20]
Regarding claim(s) 10, Zanghellini-Ramnarayan as a combination discloses: The non-transitory medium of claim 9, Zanghellini disclosing: wherein the database is a graph database. [Employing a Graph Model21]
Regarding claim(s) 13, Zanghellini-Ramnarayan as a combination discloses: The method of claim 12, Zanghellini disclosing: further comprising:
generating, by the processor, variations of the chemical or biological structure by selectively mutating an amino acid; [“mutations over the wild-type sequences”22] and
obtaining, by the processor, structural formations for the variations of the chemical or biological structure, wherein each structural formation is associated with a corresponding variation of the chemical or biological structure. [“mutations over the wild-type sequences” employing a structural entry associated with a ligand employing a transition state model23]
Regarding claim(s) 14, Zanghellini-Ramnarayan as a combination discloses: The method of claim 13, Ramnarayan disclosing [a]: wherein the simulation involves computationally simulating interactions in the target environment using the structural formations to identify native biological structures, if any, that are likely to affect activity of the chemical or biological structure when introduced to the target environment. [“The method of claim 1, wherein the binding interactions are determined by: calculating the free energy of binding between the protein structural variant and the docked drug molecule”24]
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to have modified Zanghellini, including mechanism(s) [a] as taught by Ramnarayan. One of ordinary skill would have been so motivated to employ said mechanism(s) allowing for simulation of different amino acid replacements.
Regarding claim(s) 15, Zanghellini-Ramnarayan as a combination discloses: The method of claim 12, Zanghellini disclosing: wherein the simulation measures folding and/or docking capabilities of the chemical or biological structure in the target environment, and wherein the computational workflow produces, as output, a first metric in accordance with a protein folding benchmark and/or a second metric in accordance with a molecular interaction benchmark. [“computational redesign of the wild-type amino-acid sequence is carried out, preferably through one or more iterations between computational docking and computational redesign, to obtain new sequences predicted to have the desired function”25]
Claim(s) 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zanghellini in view of Ramnarayan and further in view of Souza26.
Regarding claim(s) 11, Zanghellini-Ramnarayan as a combination discloses: The non-transitory medium of claim 9, wherein the description is formatted in accordance with the simplified molecular-input line-entry system (SMILES) format, SMILES arbitrary target specification (SMARTS) format, or International Chemical Identifier (InChI) format. [Employing SMILES27]
Before the effective filing date of the claimed invention, it would have been obvious to one of ordinary skill in the art to have modified Zanghellini, including mechanism(s) [a] as taught by Souza. One of ordinary skill would have been so motivated to employ said mechanism(s) allowing improvement to drug-target interaction screening28.
Conclusion
The prior art made of record29 and NOT relied upon is considered pertinent to applicant's disclosure:
Kalalakaran30:
Relevance of a study genetic variant observed in diagnostic subject genetic data that is associated by a clinical study with a phenotype characteristic is assessed as follows. A set of polymorphisms functionally related to the study genetic variant are identified. A foreground distribution is computed of variants observed in the diagnostic subject genetic data for the set of polymorphisms. A background distribution is computed of variants observed in genetic data of subjects of the clinical study for the set of polymorphisms. A comparison metric is computed comparing the foreground distribution and the background distribution. Relevance of the study variant to the diagnostic subject is quantified based on the comparison metric, with higher similarity of the foreground and background distributions corresponding to higher relevance
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL EZEWOKO whose telephone number is 571 272 7850. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Fonya Long can be reached on 571 270 5096. The fax phone number for the organization where this application or proceeding is assigned is 571-273-7850.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MICHAEL I EZEWOKO/Primary Examiner, Art Unit 3682
1 Claim(s) 1-8, 11-15
2 Claim(s) 9-11
3 Claim limitations comparable to a “ghost in a machine”: happening in memory of a computer but not transforming a physical substance, valid for thought experiments/scientific thought but not private ownership corresponding to patentable subject matter
4 US 10,025,900
5 US 2003/0158672
6 receiving, by a processor, input that specifies (i) a description of a chemical or biological structure, and
(ii) a target environment in which the chemical or biological structure is to be introduced
7 2:11-40
8 identifying, by the processor, a computational workflow based on the target environment
9 2:11-40
10 11:40-49
11 providing, by the processor, the description of the chemical or biological structure to the computational workflow as input, so as to initiate a simulation of the chemical or biological structure being introduced to the target environment
12 Claim 2
13 ¶319
14 4:11-18; see also 1:54-67
15 4:11-18; see also 1:54-67
16 2:11-40
17 2:11-40
18 2:11-40
19 22:39-65
20 2:11-40
21 21:1-15
22 30:7-60
23 30:7-60
24 Claim 2
25 2:11-40
26 See Form 892: Non-Patent Literature
27 Page 754
28 Page 748
29Please see Form 892 for complete listing
30 US 10,679,726
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