Notice of Pre-AIA or AIA Status
1. 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 Application, Amendments and/or Claims
2. Applicant’s response dated 3/9/2026 is considered and entered into record. Claims 1, 4-6, 8 and 11-12 have been amended. Claims 1-18 are pending.
3. Claims 16-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 24 June 2025.
4. Claims 1-15, drawn to a method of predicting therapeutic efficacy of compounds based on identification of features in electrically-excitable cells, are considered for examination in the instant application.
Withdrawn Objections/Rejections
5. Upon consideration of proper amendment of claims 1, 6, 11 and 12, the objections are withdrawn.
6. Upon consideration of appropriate amendment of claims the rejection under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn.
7. Upon consideration of amendment of claims, nonstatutory double patenting rejections are withdrawn.
Rejections maintained
Claim Rejections - 35 USC § 102
8. 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.
9. Claims 13-15 are rejected under AIA 35 U.S.C. 102(a)(1) as being anticipated by Eggan et al US PGPB 20190025291, 1/24/2019. The rejection is maintained for reasons of record in the Office Action dated 12/9/2025.
It is noted that upon consideration of the amendment of claims 1, 6 and 8, previously rejected claims 1-12 are not included in the present 102 rejection.
10. Claim 13 recites a method for drug discovery comprising identifying therapeutically efficacious action potential (AP) features, exposing a neuron to a test compound and stimulating the neuron for firing an AP, determining the AP features, and identifying the test compound as a putative therapeutic compound (PTC) against the neuronal disease if the AP features of the stimulated neuron match the identified features; wherein: the identifying AP features comprises stimulating diseased and healthy neuronal cells to fire AP, identifying the AP features, and determining APs exclusive to diseased and/or to healthy cells (claim 14); and stimulating neuronal diseased cell to fire APs in the presence and absence of a therapeutic compound, identifying AP features that are different in the presence of the compound (claim 15).
11. Eggan et al teach a method for drug discovery using compound screening, comprising identifying signature (features) of action potential in neurons of normal and diseased cell (including spike trains), treating cells with a compound to transmit (fire) an action potential, comparing the features with those of the stimulated cell, determining that the compound will promote “a normal-type phenotype” (matching), and identifying the compound for treating the disease (putative therapeutic compound) (para 0006, 0013, 0014, 0015, 0018, 0020) (instant claims 13, 14). The reference teaches the use of compound controls (absence of therapeutic compound) with associated signature, and determines the difference or match with the control signature (para 0213, 0216, 0221, 0014, 0018) (instant claim 15).
12. The reference therefore, anticipates the claimed method.
Applicant’s remarks:
13. Asserting that the amendment of claim 1 requires mapping or comparing AP features of a putative therapeutic compound against substantially identical features of known therapeutic compounds, Applicant argues that Eggan does not disclose a comparison of AP features from known therapeutic compounds with those derived from PTCs, and prediction of efficacy by matching said features. Alleging a structural difference between the method of instant claim 1 and Eggan teachings, Applicant asserts that while instant claim requires “a drug-against-drug comparison”, Eggan teaches a “drug-against-baseline comparison” (i.e. comparing signatures of a compound treated cell to signatures of an untreated cell). Applicant argues that even though Eggan (para 0205) teaches various signatures including electrophysiology parameters, the reference does not teach mapping into a “reduced-dimensionality feature space”. Applicant concludes that Eggan therefore, does not teach each and every element of amended claim 1. Applicant adds that since Eggan does not teach “drug-against-drug” comparison recited in independent claims 6, 8 and 13, these claims as well as dependent claims therefrom are not anticipated. Applicant therefore, requests withdrawal of the 102 rejection.
14. Applicant’s arguments are fully considered, and found to be persuasive in part. Applicant’s remark stating that Eggan does not teach drug against drug comparison recited in independent claims 1, 6, and 8, is found to be persuasive. Upon consideration of amendment of independent claims 1, 6 and 8 to recite “known” therapeutic compounds, and amendment of claims 4, 5 and 11 to recite “reduced-dimensionality space”, the 102 rejection for claims 1-12 as anticipated by Eggan is withdrawn. A new 103 rejection necessitated by amendment has been set forth.
15. Applicant’s arguments that independent claim 13 is not anticipated by Eggan is considered, but not found to be persuasive. Claims 13-15 are not amended, and contrary to Applicant’s contention, claim 13 does not recite “drug-against-drug” comparison (i.e. comparison with a known therapeutic compounds). Therefore, the claims stay anticipated over the teachings of Eggan.
New Rejections – necessitated by amendment
Claim Rejection - 35 USC § 103
16. 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.
17. Claims 1-15 are rejected under AIA 35 U.S.C. 103 as being unpatentable over Eggan et al (2019), in view of Suzuki et al US 2021/0319853, PCT filing date 9/27/2019.
18. The claims are directed to a method for predicting therapeutic efficacy comprising identifying action potential features of electrically excitable cells in the presence of a putative therapeutic compound; mapping said features against substantially identical features present in stimulated neuronal cells treated with known therapeutically active compounds (KTC) in a diseased cell; predicting efficacy of the putative therapeutic compound (PTC) based upon matching of identified features with the features treated with KTCs (claim 1); wherein the method further comprises: predicting side effects of said PTC (claim 2); identifying action potentials (AP) in the presence of a second PTC; mapping said features against those of control cells; predicting efficacy of a combination of the first and second PTC against said disease based upon matching of identified features with the features treated with known compounds (claim 3). Claim 4 recites that the mapping step comprises mapping of the action potentials onto a reduced-dimensionality space occupied by the neural cells in the presence and absence of the PTC. Claim 5 recites that the predicting step comprises identifying (and comparing) regions of the reduced-dimensionality space occupied by the neural cells in the presence and absence of the efficacious compound, and determining the extent the regions for the putative therapeutic and efficacious compounds overlap. Claim 6 recites a method for characterizing a therapeutic effect comprising identifying action potential features of stimulated electrically excitable disease cell in the absence of a therapeutic compound; stimulating the cell with a KTC and identifying the features in the presence of the compound; determining if the features differ from those in the absence of the compound and characterizing a therapeutic effect; the method further comprising screening a library of PTCs that causes a differing action potential (claim 7). The claims also recite a method for identifying compounds having therapeutic efficacy, comprising identifying APs present in stimulated neuronal cells in the presence of a KTC, and absent without the KTC; stimulating neuronal cells in the presence of a PTC; matching APs in said stimulated neuronal cells with those present in cells exposed to said KTC and identifying the PTC (claims 8, 12); wherein: one or more identified features correlate with a side effect (claim 9); the neuronal cells are stimulated in the presence of a combination of PTCs (claim 10); and the mapping of APs is done onto a reduced-dimensionality space defined by AP features (claim 11).
19. The teachings of Eggan et al are set forth above.
20. Eggan et al also teach high-throughput methods for drug screening (para 0155, 0227). The reference teaches obtaining a signature including AP features of cells or neurons at baseline, with different stimuli (stimulated), before and after exposure to therapeutic compound or its controls (para 0205, 0213), exposing (stimulating) neuronal cells with a (putative) therapeutic compound (para 0216), comparing the signature and determining the difference or matching with the control signature for identification of a candidate compound or combination of compounds (putative therapeutic compound/s) (para 0221, 0216) (instant claims 1, 3, 8, 10, 12), wherein the data comprising signal processing, APs and other electrophysiology parameters are mapped as clusters (space) (para 0188, 0205, 0019, 0013) (instant claims 4, 5, 11). Even though Eggan et al do not teach the term “reduced-dimensionality” space, the reference teaches that a compound or combinations affecting a "change in phenotype from disease-type to normal" is a (putative) candidate compound (para 0216), which potentially would correspond to identifying regions of "reduced-dimensionality space" of instant claims 4, 5 and 11. Please note that the instant specification (page 10, para 1, 2; page 13, lines 13-17) teaches that dimensions correspond to features or attributes (e.g. AP), and reduced dimensionality space would be a more concise or succinct number of features. Since the reference teaches suitability of treatment (i.e. efficacy of candidate compounds) based upon firing pattern (or AP) as the only parameter, the reference reasonably indicates the mapping and identification of reduced dimensionality space. Since Eggan et al teach the identification of a candidate therapeutic compound “to determine suitability of a treatment prior to application to patient” having a neuronal disease (para 0216) using the same method parameters as instantly claimed, the reference teaches the method of predicting therapeutic efficacy and characterizing a therapeutic effect of instant claims 1, 6 and 8.
21. Eggan et al further teach the generation and use of an optical signature comprising action potentials of a diseased neuron from a patient in response to neural stimulation (identifying features in the absence of a therapeutic compound); exposing the cell to a therapeutic compound and identifying the effect (features) of the compound “based on the obtained signature” (characterizing a therapeutic effect) (Abstract; para 0014; 0020). The reference teaches obtaining the features before, during and after testing the therapeutic and controls (para 0213), and using different compounds or screening a library of compounds that causes an effect on the electrical activity or action potential features of the cells (para 0217, 0227, 0155) (instant claims 6, 7).
22. Eggan et al do not explicitly mention “known” therapeutic compounds of instant claims. The reference however, teaches the use of tool or test compounds in the methods of the invention, wherein tool compounds are “known”, and can achieve “greater specificity” in “determining disease mechanisms” (para 0212, 0214). As also taught in the instant specification (page 39, para 1), tool compounds are known drugs (known therapeutic compound) that are used in the screening assay.
23. Eggan et al do not specifically teach mapping or comparing action potential features of PTC against those obtained from KTCs, and predicting efficacy of the PTC based upon the action potentials obtained from known compounds (substantially identical features).
24. Suzuki et al teach a method for predicting the characteristics or property of a target or unknown compound (putative therapeutic compound) comprising: receiving (identifying) activity (features) data on nerve cells (neurons) for the target compound; converting the data into an image (identified features) and inputting the image into an image recognition model comprising images from the activity data (substantially identical features) on nerve cells obtained from a plurality of known compounds (mapping); and processing the image in the image recognition model and determining (predicting) at least one characteristic (property) of the target compound (Abstract; Fig. 9, 10; para 0007, 0015-0016; 0069-0073; 0098), wherein: the activity of a neuron can be membrane potential or activity potential (such as action potential) (para 0008, 0113); the property comprises efficacy or toxicity of the target compound (para 0067, 0080, 0134); and toxicity refers to an unfavorable effect (side effect) of the agent (compound) (para 0100) (instant claim 1, 2, 8, 9). Suzuki et al also teach the restriction of features characteristic to a known compound with lesser dimensional features (reduced dimensionality space), which can be used in prediction of property (of the target compound), by determining a feature that is similar to that of the known compound, and excluding an outlier value (determining the extent of overlap of the identified regions) (para 0178, 0179, 0192) (instant claims 4, 5, 11). In another embodiment (Items 10, 11), the reference teaches property prediction comprising converting the activity of a neuron in response to known compounds into an image, processing the image and normalizing said features with that obtained prior to administration of the known compounds (determining whether the features in the presence of the known compound differ from those in the absence of the compound) (paras 0019-0022) (instant claim 6).
25. It would have been, therefore, obvious to the person having ordinary skill in the art before the effective filing date of the claimed invention to modify the method of predicting or identifying the therapeutic efficacy of a PTC by comparing action potential features of the compound treated neurons with compound controls or untreated cells as taught by Eggan et al, by comparing features of activity of target (PTC) compounds on neurons with that of known compounds, in view of the teachings of Suzuki et al. The person of ordinary skill would have been motivated to use known compounds in the screening method as known compounds (or tool compounds) can achieve “greater specificity” in “determining disease mechanisms” (Eggan et al). The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references, before the effective filing date of the instant invention.
26. Thus, the claimed invention as a whole was prima facie obvious over the combined teachings of the prior art.
Double Patenting
27. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
28. A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
29. The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
30. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
31. Claims 1-15 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 13 and 14 of co-pending application number 17/842,352 in view of Suzuki et al (2019).
Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to a method of identifying features of neural activity in the presence of a therapeutic or a combination of therapeutics (compound or antisense oligonucleotides), comparing (mapping) with the data store of neural activity in neurological conditions (diseased cell), predicting toxicity (side effects) and identifying a candidate therapeutic that does not induce toxicity (predicting efficacy), wherein the cells comprise an optical reporter (i.e. the cells are stimulated by light) for generating neural activity. Note that the “data store includes a phenotypic 30,000 compound screen from human iPSC-neurons”, using a neuronal disease model, no-drug control (absence of therapeutic) and a reference library of drug fingerprints (known therapeutic compounds) (‘352 PGPB, para 0094, 0103).
The only differences between the two sets of claims are:
(i) Instant claims recite action potential, while ‘352 claims only recite “neural activity”. However, this would be obvious in view of the ‘352 specification teaching that blue light triggers the firing of action potential (neuronal electrical activity) (para 0072, 0075, 0076).
(ii) ‘352 claims recite antisense oligonucleotides as therapeutic, while instant claims do not recite oligonucleotides. However, the instant claims recite a genus of therapeutic compounds.
(iii) Instant claims 4, 5 and 11 recite that mapping is onto a reduced-dimensionality space, while the ‘352 claims do not have this limitation. However, this would be obvious in view of the teachings of Suzuki et al. for reasons stated in this office action. Moreover, the ‘352 PGPB teaches a comparison of a test drug and a known drug, and mapping by “fingerprint similarity in the reduced drug space” (para 0103).
32. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
33. Claims 1, 4, 13-14 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-6 and 8-9 of co-pending application number 17/735799.
Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to a method of identifying (recording) features of action potentials exhibited by electrically active cells (with and without a pathology) (mapping or recording), exposing the cells to a test compound and identifying the phenotype of not having the pathology with exposure to test compound (claims 4, 5) (predicting efficacy and identifying the compound as a putative therapeutic compound (PTC)).
The only differences between the two sets of claims are:
(i) Instant claim 4 recites mapping of APs onto a reduced dimensionality space, while ‘799 claims do not recite this limitation. However, the ‘799 spec teaches that the identified AP features are mapped onto a “lower-dimensional space” (graphical) (para 0103; Fig 8).
(ii) Instant claim 1 recites mapping (comparing) AP features of PTC with known therapeutic compounds (KTC), while the ‘799 claims do not recite “known” compounds. However, claims 1 and 5 of the ‘799 application recite using a machine learning system for comparison of AP after exposure to a test compound (claim 5), wherein the machine learning system comprises data having recordings from known compounds with known efficacy (para 0014 of the ‘799 PGPB).
34. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
35. Claims 1, 6-7 and 13-15 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 13-16, 18 and 20-22, of US Patent 10,613,079 in view of Suzuki et al (2019). Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to a method comprising stimulating an electrically active (excitable) cell or neuron from neurological disease, exposing the cell in the presence or absence of a compound, and comparing the signal with a control.
The only differences between the two sets of claims are:
(i) Instant claims recite identifying therapeutic efficacy or effect of the compound, while the ‘079 claims do not have this limitation. However, this would be obvious in view of the ‘079 PGPB which teaches observation of a response relative to a control cell could be applied to compound screening and determining therapeutic efficacy (para 0013, 0014, 0015, 0018).
(ii) Instant claims recite identifying action potential, while ‘079 claims do not mention action potential. However, the ‘079 specification (para 0013) suggests that the signal could be in the form of action potential.
(iii) Instant claims 1 and 6 recite mapping (comparing) AP features of PTC with known therapeutic compounds (KTC), while the ‘079 claims do not recite “known” compounds. However, the ‘079 specification (para 0212, 0214) teaches the use of tool compounds having known efficacy on neuronal activity. Also, the use of KTC for predicting therapeutic efficacy of a PTC would be obvious in view of the teachings of Suzuki et al, as stated in this office action.
36. Therefore, the instant claims are not patentably distinct over the issued claims in U.S. patent 10,613,079.
37. Claims 1, 3-8 and 10-15, are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 7-11, of US Patent 9,594,075, in view of Suzuki et al (2019).
Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to a method of determining the effect of a compound on a neurological condition (therapeutic efficacy) comprising presenting or exposing a neuron or stimulated neurons (diseased or normal) to a compound or plurality of compounds, identifying and comparing the signal to a control signal (mapping) and identifying the compound as a candidate for treatment (putative therapeutic compound) based upon the analysis of the signal with respect to control signal, wherein the signal can be a spike train produced by the neuron (claim 10 of ‘075 patent). It is noted that spikes are associated with action potential as also suggested in the ‘075 PGPB (para 0013), as well as is evident from the instant specification (page 8, line 23; page 9, para 1).
The only differences between the two sets of claims are:
(i) Instant claims 1 and 6 recite mapping (comparing) AP features of PTC with known therapeutic compounds (KTC), while the ‘075 claims do not recite “known” compounds. However, the ‘075 specification (para 0213, 0215) teaches the use of tool compounds having known efficacy on neuronal activity. Also, the use of KTC for predicting therapeutic efficacy of a PTC would be obvious in view of the teachings of Suzuki et al, as stated in this office action.
(ii) Instant claims 4, 5 and 11 recite that mapping is onto a reduced-dimensionality space, while the ‘075 claims do not have this limitation. However, this would be obvious in view of the teachings of Suzuki et al. for reasons explained in the 103 rejection.
38. Therefore, the instant claims are not patentably distinct over the issued claims in U.S. patent 9,594,075.
Applicant’s Remarks:
39. Applicant requests that the rejections on grounds of nonstatutory obviousness-type double patenting be held in abeyance until the claims are in condition for allowance.
40. The rejections have not been overcome by amendment or the filing of an approved terminal disclaimer. Thus, the rejections are modified and presented as necessitated by amendment.
Conclusion
41. No claims are allowed.
42. Applicant’s amendment necessitated the new ground(s) of rejection presented in the Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
43. A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no, however, event will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
44. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Aditi Dutt whose telephone number is (571)272-9037. The examiner can normally be reached on M-F 9:00am-5:00pm.
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/A. D./
Examiner, Art Unit 1675
28 April 2026
/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675
Prosecution Insights