DETAILED ACTION
Claim Status
Claims 1-15 are rejected.
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 .
Priority
This application claims Foreign Priority to application # EP22179854.9 , filed 06/20/2022. Foreign Priority is acknowledged. Therefore, the effective filing date of claims 1-15 is 06/20/2022. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The Information Disclosure Statement(s) filed on 09/05/2023 is in
compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of list of
references cited from each IDS is included with this Office Action.
Drawings
The drawings filed on 06/09/2023 are accepted.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 14 rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 14 recites iteratively repeating the steps of claim 12, but there are no active steps recited in claim 12, only alternative additional steps.
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 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more.
In accordance with MPEP § 2106, claims found to recite statutory subject matter ( Step 1 : YES) are then analyzed to determine if the claims recite any concepts that equate to an abstract idea, law of nature or natural phenomenon (Step 2A, Prong 1). In the instant application, the claims recite the following limitations that equate to an abstract idea:
1, 15. determining information about the biological sample and the analytes, the analytes being marked by a plurality of markers
1, 15. generating a probabilistic model of a distribution of the analytes within the biological sample based on the determined information
1, 15. determining a presence of at least one analyte in the at least one optical readout based at least partially on the probabilistic model of the distribution of the analytes within the biological sample.
2.The method according to claim 1, wherein the information about the sample is determined from at least one of generic databases or data generated from the biological sample.
3.The method according to claim 1, wherein the information about the sample comprises at least one of the following types: genomic, transcriptomic, proteomic, metabolomic, interactomic, localisomic, and/or epigenomic.
4.The method according to claim 1, wherein the information about the sample is determined for at least one of the following levels: subcellular, organellular, cellular, and/or tissular.
5. The method according to claim 1, wherein the information about the sample is determined prior to generating the at least one optical readout.
6. The method according to claim 1, wherein the at least one optical readout is segmented in order to determine the information about the sample.
7. The method according to claim 6, wherein the information about the sample is determined from the optical readout pixel-per-pixel.
8. The method according to claim 6, wherein the probabilistic model is modified based on the information about the biological sample determined from the at least one optical readout.
10. The method according to claim 1, wherein the plurality of markers is based on the probabilistic model of the distribution of the analytes.
The limitations for “determining” and “generating” refer to mathematical actions over sets of data, recited so broadly that there are embodiments which could be performed by a human being with a pen and paper. The dependent limitations only modify the types of data to be manipulated. Therefore, these limitations fall under the “Mental process” and “Mathematical concepts” groupings of abstract ideas. While claim 15 recites performing some aspects of the analysis with a “computer”, there are no additional limitations that indicate that this computer requires anything other than carrying out the recited mental process or mathematical concept in a generic computer environment. Merely reciting that a mental process is being performed in a generic computer environment does not preclude the steps from being performed practically in the human mind or with pen and paper as claimed. If a claim limitation, under its broadest reasonable interpretation, covers performance of the limitation in the mind but for the recitation of generic computer components, then if falls within the “Mental processes” grouping of abstract ideas. As such, claims 1-15 recites an abstract idea ( Step 2A, Prong 1 : YES).
Claims found to recite a judicial exception under Step 2A, Prong 1 are then further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not (Step 2A, Prong 2). This judicial exception is not integrated into a practical application because the claims do not recite an additional element that reflects an improvement to technology or applies or uses the recited judicial exception to effect a particular treatment for a condition. Rather, the instant claims recite additional elements that amount to mere instructions to implement the abstract idea in a generic computing environment or mere instructions to apply the recited judicial exception via a generic treatment. Specifically, the claims recite the following additional elements:
1, 15. generating at least one optical readout of the biological sample
9. The method according to claim 1, further comprising generating at least one further optical readout, wherein the analytes are marked by a further plurality of markers for the at least one further optical readout.
11.The method according to claim 1, wherein generating the at least one optical readout comprises: i) providing the plurality of markers comprising a plurality of affinity reagents, each affinity reagent configured to attach to one of the analytes, and a first plurality of combinations of dyes, each combination of dyes being unique within the first plurality of combinations of dyes, and each combination of dyes comprising at least two dyes having different characteristics for at least one of excitation and/or emission, wherein each combination of dyes is attached to an associated affinity reagent according to a first mapping, ii) directing excitation light at the sample, the excitation light having characteristics for exciting the at least two dyes having different characteristics for at least one of excitation and/or emission, and iii) generating at least one first optical readout from emission light emitted by the excited dyes.
12. The method according to claim 11, further comprising at least one of: deactivating at least one of the dyes in the first plurality of combinations of dyes, removing the attachment between at least one affinity reagent and at least one of the combinations of dyes, removing the attachment between at least one affinity reagent and at least one of the analytes, waiting longer than a fluorescence lifetime of at least one of the dyes in the first plurality of combinations of dyes; and/or repeating steps i) to iii) of claim 11 for a second plurality of combinations of dyes or for the first plurality of combinations of dyes according to a second mapping, the second plurality of combinations of dyes being different from the first plurality of combinations of dyes, the second mapping being different from the first mapping.
13. The method according to claim 12, further comprising: providing at least one dye and/or combination of dyes for the second plurality of combinations of dyes, and/or providing rules for the second mapping, based on the at least one first optical readout.
14.The method according to claim 12, further comprising iteratively repeating the steps of claim 12 for at least one of: a number of pluralities of combinations of dyes, or a number of mappings, until all affinity reagents attached to analytes in the sample are determined.14.The method according to claim 12, further comprising iteratively repeating the steps of claim 12 for at least one of: a number of pluralities of combinations of dyes, or a number of mappings, until all affinity reagents attached to analytes in the sample are determined.
15. A non-transitory computer-readable medium having program steps stored thereon, the program steps, when executed by a computer processor, causing performance of a method for analysing a biological sample with a plurality of analytes
The limitation for the optical readout is a form of mere data gathering, similar to selecting information, based on types of information and availability of information in a power-grid environment, for collection, analysis and display, Electric Power Group, LLC v. Alstom S.A., 830 F.3d 1350, 1354-55, 119 USPQ2d 1739, 1742 (Fed. Cir. 2016). There are no limitations that indicate that the claimed computer or the formats of the provided data require anything other than generic computing systems. As such, these limitations equate to mere instructions to implement the abstract idea on a generic computer that the courts have stated does not render an abstract idea eligible in Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. As such, claims 1-15 are directed to an abstract idea ( Step 2A, Prong 2 : NO).
Claims found to be directed to a judicial exception are then further evaluated to determine if the claims recite an inventive concept that provides significantly more than the judicial exception itself (Step 2B). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment. The instant claims recite additional elements enumerated above, in the section on step 2A.
The limitation for generating the optical readout is well understood, routine and conventional, as these elements are described by Danial et al. (Global Cardiology Science and Practice 2016:16). Danial discusses adding dye markers to analytes and detecting them with excitation light (pg 1 ¶ 2), deactivation and removal of dye as an intermediary step in the analysis process (pg 14 ¶ 1), and iterative repetition (pg 12 fig. 9). As discussed above, there are no additional limitations to indicate that the claimed computer requires anything other than generic computer components in order to carry out the recited abstract idea in the claims. Claims that amount to nothing more than an instruction to apply the abstract idea using a generic computer do not render an abstract idea eligible. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. The additional elements do not comprise an inventive concept when considered individually or as an ordered combination that transforms the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself ( Step 2B : No). As such, claims 1-15 are not patent eligible.
Claim Rejections - 35 USC § 103
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 filing 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.
Claims 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Nino et al. (Biophysical Journal 112, 1777–1785, May 9, 2017, henceforth “Nino”), as evidenced by Oxford English Dictionary (Oxford University Press, 2008).
Regarding claim 1, Nino teaches using superresolved location microscopy (pg 1777 right col ¶ 3) to determine information about multiple tagged/marked analytes on a single fluorophore (abstract) to determine presence of analytes from optical readouts, using a probabilistic model (pg 1779 left col ¶ 1).
Regarding claim 2, Nino provides instructions for generating data from the biological sample (pg 1779 right col ¶ 9).
Regarding claim 3-4, Nino used subcellular genomic data (pg 1779 right col ¶ 9).
Regarding claim 5, multiple “blinks” are measured to generate the optical readout (pg 1779 right col ¶ 9).
Regarding claim 6, images are processed into a “localization table,” segmenting the image data into a table to determine counts (pg 1780 right col ¶ 1).
Regarding claim 7, the analysis is pixel-per-pixel (pg 1782 left col ¶ 1).
Regarding claim 8, the number of molecules in the biological sample is part of the probabilistic model of Nino (pg 1779 left col ¶ 4).
Regarding claim 9, Nino provides for each analyte having multiple fluorophores and for the experiment to be repeated (pg 1782 left col ¶ 1).
Regarding claim 10, Nino’s model is a simulated experiment. A real-world implementation of Nino would be based on the probabilistic models shown that optimized the model (pg 1780 right col ¶ 1).
Regarding claim 11, Nino’s model accounts for immunolabeling with multiple dyes. Immunolabeling is used to detect and localize unique antibodies using dyes (“Immunolabeling,” Oxford English Dictionary 2008). Antibodies are a type of affinity reagent, because they bind to targets.
Regarding claim 12, MPEP 2144.04.II.A states that omission of an element and its function is obvious if the function is not desired. Removal of a dye and repeating the analysis is obvious if the experimenter does not want to detect the previously dyed molecules. Nino provides for repeating the experiment (pg 1782 left col ¶ 1).
Regarding claim 13, Nino instructs one to run the analysis, “bunch together blinks that last for multiple frames,” (pg 1782 left col ¶ 1). and to repeat the analysis. This is an example of providing rules for a second mapping based on a first optical readout.
Regarding claim 14, Nino writes: “From 25 realizations of this experiment, our measurements yielded 45 +- 9 molecules with the actual number of molecules fixed at 49.” In the second box of fig. 5, one can see the result of an experiment where exactly 49 molecules were determined.
Claim 15 is a restatement of claim 1, the only difference being that it is directed to a “non-transitory computer-readable medium” rather than a method. The arguments against claim 1 apply, mutatis mutandis.
Regarding claims 1-15, An invention would have been prima facie obvious to one of ordinary
skill in the art at the time of the effective filing date of the invention if some teaching, suggestion, or motivation in the prior art would have led that person to combine the prior art teachings to arrive at the claimed invention. There is an implicit suggestion to remove a fluorophore in the text of Nino. There would be a reasonable expectation of success in making this combination to a person of ordinary skill in the art, as it is explained in the MPEP 2144.04.II.A that omission of an element and its function is obvious if the function is not desired. Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time to modify the method of Nino by removing a fluorophore, in order to repeat the analysis without undesired fluorophores.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GRACELYN M HILL whose telephone number is (571)272-9871. The examiner can normally be reached Monday-Friday 8:30-5pm.
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/G.M.H./Examiner, Art Unit 1685
/OLIVIA M. WISE/Supervisory Patent Examiner, Art Unit 1685
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