DETAILED ACTION
Applicant’s response, filed 27 May 2026, has been fully considered. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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
Status of Claims
Claims 7, 27, and 36 are cancelled.
Claims 1-6, 8-26, and 28-35 are pending.
Claims 1-6, 8-26, and 28-35 are rejected.
Claims 17, 21, and 35 are objected to.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Accordingly, the effective filing date of the claimed invention is 11 June 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 27 May 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the list of cited references was considered in full by the examiner.
Drawings
The replacement drawing sheets filed 27 May 2026 have been entered.
The drawings filed 27 May 2026 objected to because:
The view numbers must be larger than the numbers used for reference characters. See 37 CFR. 1.84(u)(2). The view numbers for FIG. 1-11 are not larger than the numbers used for reference characters. Increase the font size of the view numbers accordingly.
It is not clear which portions of the figure for FIG. 2A and FIG. 2B actually correspond to FIG. 2A and FIG. 2B respectively. 37 CFR 1.84(u)(1), states partial views intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter. Here, the partial views are not clearly delineated. If Applicant intends for figure 2 to be one complete view, the letters for “A” and “B” should be removed and FIG. 2A and FIG. 2B should simply be labelled FIG. 2. Otherwise, Applicant must clearly separate which parts of the figure correspond to FIG. 2A and FIG. 2B.
It is not clear which portions of the figure for FIG. 11A-D actually correspond to FIG. 11A-D respectively, for similar reasons discussed above for FIG. 2A and FIG. 2B. For example, are the arrows pointing upwards from the various boxes adjacent to the large “b” part of FIG. 11B or part of FIG. 11A?
FIG. 8 includes reference character 12 which is not mentioned in the description, and thus fail to comply with 37 CFR 1.84(p).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Response to Arguments
Applicant's arguments filed 27 May 2026 regarding the drawing objections have been fully considered but they are not persuasive.
Applicant remarks replacement sheets for Figures 1-3, 5, 8, 10, and 11 are filed which correct the view numbers, and that the numerals in Figures 6-8 are removed in the replacement sheets (Applicant’s remarks at pg. 10, para. 2-4).
This argument is not persuasive. The view numbers for various figures, identified above, do not clearly label which partial views correspond to which view number, and furthermore, the view numbers are not larger than the reference characters. Furthermore, FIG. 8 still includes reference character 12. Therefore, the objection to the drawing is maintained.
Specification
References to Applicant’s specification are made with respect to the published version.
The amendment to the specification filed 27 May 2026 has been entered.
The objection to the disclosure for containing an embedded hyperlink and/or other form of browser-executable code in the Office action mailed 30 Dec. 2025 has been withdrawn in view of the amendments to the specification filed 27 May 2026.
The objection to the abstract for containing phrases which can be implied and for not describing steps of the process in the Office action mailed 30 Dec. 2025 has been withdrawn in view of the replacement abstract received 27 May 2026.
However, abstract filed 27 May 2026 is objected to for the following reasons:
The abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b). A new abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text.
Claim Objections
The objection to claims 5, 7, 9, 11, and 20 in the Office action mailed 30 Dec. 2025 has been withdrawn in view of claim amendments received 27 May 2026.
Claims 17, 21, and 35 are objected to because of the following informalities. This objection is newly recited.
Claim 17 recites “The method of claim 15: wherein the available treatments are…; the available treatments include….; and/or the available treatments include…”, which should be amended to include a wherein before each member of the list to correct grammar, thus reciting “The method of claim 15: wherein the available treatments…; wherein the available treatments include drug…; and/or wherein the available treatments include a modified code…”.
Claim 21 recites “The method of claim 20, wherein further comprising performing genetic sequencing is performed…”, which is grammatically incorrect. The claim should be amended to correct grammar (e.g. “wherein genetic sequencing is performed..”, or “The method of claim 20, further comprising performing genetic sequencing for…”, etc);
Claim 35 recites “The method of claim 21, wherein further comprising adjusting, by a user, one or more (a)-(i) to dynamically determine…are adjustable by a user…”, which is a grammatical error and nonsensical. The claim should be amended to recite “The method of claim 21, further comprising adjusting, by a user, one or more (a)-(i) to dynamically determine…for the subject
Appropriate correction is required
Response to Arguments
Applicant's arguments filed 27 May 2026 regarding the claim objections have been fully considered but they do not pertain to the newly recited objection set forth above.
Claim Interpretation
Claim 1 recites the term “optionally”. Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed. See MPEP 2111.04 I. Therefore, any limitation following “optionally” is interpreted to be not required by the claim.
Claim 33 recites “…storing on a non-transitory memory the plurality of EMRs, the plurality of phenomes, and the plurality of clinical phenotypes of the plurality of subjects to generate a searchable database”. The phrase “to generate a searchable database” is interpreted to recite an intended use of the stored EMRs, phenomes, and clinical phenotypes, but the claim does not require generating a searchable database. It is noted that claim 34 does then utilize the database, and thus claim 34 is interpreted to require that the database is generated.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1-6, 8-26, and 28-35 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention. This rejection is newly recited and necessitated by claim amendment.
Claim 1, and claims dependent therefrom, recite “h) analyzing the results of (f) and (g) to generate a third list of potential differential diagnoses of the subject by integration the efficacy and quality of evidence of the available treatments determined in step (g) with the second list of potential differential diagnoses…”.
Claim 16 recites “…the available treatments of step (g) are utilized to generate a probabilistic diagnoses ranked based on efficacy and quality of evidence of efficacy for each of the potential differential diagnoses in the second list”.
Claim 18 recites “wherein the third list of potential differential diagnoses is generated by comparing the second list of potential differential diagnoses with the available treatments of step (g)…”.
MPEP 2163.04 I states a simple statement such as "Applicant has not pointed out where the new (or amended) claim is supported, nor does there appear to be a written description of the claim limitation ‘____’ in the application as filed." may be sufficient where the claim is a new or amended claim, the support for the limitation is not apparent, and applicant has not pointed out where the limitation is supported.
In the instant case, Applicant states that support for all the claim amendments are found throughout the application and claims as originally filed, at least at [0046] and the cancelled claims (Applicant’s remarks at pg. 10, para. 1). Applicant’s arguments filed 27 May 2026 at pg. 20, para. 2 further states the specifically provides support for amendment to claim 1 at para. [0046] and [00195] as filed.
Applicant’s specification at para. [0065] as published (corresponding to [0046] as filed) discloses that the method includes determining the efficacy and/or quality of evidence of efficacy of available treatments for the list of potential differential diagnoses, and in various aspects the generated list of potential differential diagnoses of the subject is rank ordered and accompanied by the suitable available treatments”. While this provides support for analyzing a list of potential differential diagnoses and accompanying the list with suitable treatments after determining available treatments, this does not provide support for the specific limitations of “…generate a third list…by integrating the efficacy and quality of evidence of efficacy of the available treatments…with the second list of potential diagnoses…”. Applicant’s specification at para. [0206] as published (corresponding to [00195] as filed), only generally discloses that expert reviewers evaluated interventions to determine efficacy and a level of published evidence for each intervention; however, this does not provide support for how this efficacy and evidence information may have been integrated into the second list to generate the third list. Overall, there is no mention in the specification of specifically integrating (meaning to bring together into a whole or blending) the efficacy and quality of evidence of efficacy information with the second list as claimed to generate a third list. At best, the specification (see para. [0050]-[0052]) provides support for generally analyzing the results of (f) and (g) (i.e. analyzing the second list and the efficacy and quality of evidence information) to generate a third list, as recited in the original claims. However, there is no requirement for specific integration of efficacy or quality of evidence information with the second list, and it is not apparent where this is support for the narrowing claim language added to claim 1, discussed above.
Similarly, with respect to claims 16 and 18, while the specification states that the third list is “rank ordered, together with available treatments”, the specification does not specifically disclose rank ordering the third list based on efficacy and quality of evidence of efficacy for each of the potential differential diagnoses in the second list and/or by specifically comparing the second list with the available treatments. The only mention of “quality of evidence of efficacy” in the specification is at para. [0014], [0049], [0065], and original claim 1, which only discuss determining quality of evidence of efficacy, but do not discuss that the third list is specifically ranked based on this information.
For the reasons discussed above, the specification does not provide a sufficient disclosure of the limitation above recited in claims 1-6, 8-26, and 28-35 to demonstrate to one of ordinary skill in the art that the inventor possessed the invention at the time the application was filed. THS IS A NEW MATTER REJECTION. For more information regarding the written description requirement, see MPEP §2161.01- §2163.07(b).
Claim Rejections - 35 USC § 112(b)
The rejection of claims 7, 27, and 36 under 35 U.S.C. 112(b) in the Office action mailed 30 Dec. 2025 has been withdrawn in view of the cancellation of these claims received 27 May 2026.
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.
Claims 1-6, 8-26, and 28-35 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention. Any newly recited portion is necessitated by claim amendment.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “available treatments” in both steps g) and h). The term “available” is a relative term which renders the claim indefinite. The term “available” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As a result, the metes and bounds of what treatments fall within the metes and bounds of an “available” treatment are not clear. For example, it is not clear if “available treatments” is intended to refer to simply any treatment that could be administered (e.g. pre-clinical treatments), or if the term refers to treatments available to everyone (e.g. clinically approved). Similarly, it is unclear if the term refers to “available” treatments as of the effective filing date of the claimed invention, or if the term refers to any treatment currently “unavailable” but later becomes available. For purpose of examination, the term “available treatment” is interpreted to mean “treatment”.
Claim 1, and claims dependent therefrom, are indefinite for recitation of “h)…by integrating the efficacy and quality of evidence of efficacy of the available treatments determined in step (g)”. However, claim 1 previously recites “g) determining the efficacy and/or quality of evidence of efficacy of available treatments for the second list…”. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 1 recites the broad recitation “determining the efficacy and/or quality of evidence of efficacy of available treatments for the second list”, and the claim also recites “the efficacy and quality of evidence of efficacy of the available treatments” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. In other words, it is not clear if step g) requires both the efficacy and quality of evidence of efficacy are determined (suggested by step h), or if step g) only requires efficacy or quality of evidence of efficacy to be determined (suggested by step g). For purpose of examination, step h) is interpreted to mean “by integrating the efficacy and/or quality of evidence of efficacy…determined in step (g)”, consistent with step g).
Claim 8 is indefinite for recitation of “all known genetic diseases”. The metes and bounds of “all known genetic diseases” because it is not clear as to whom or when, the genetic diseases are known. As a result, one of ordinary skill in the art cannot ascertain the metes and bounds of “all known genetic diseases” For purpose of examination the term is interpreted to mean “of genetic diseases expressed in the same vocabulary…”.
Claim 10 is indefinite for recitation of “…wherein the genetic variants are utilized to generate a probabilistic diagnosis”. examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are "wherein" clauses. The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a "wherein" clause limited a process claim where the clause gave "meaning and purpose to the manipulative steps"). However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited. See MPEP 2111.04 I. In the instant case, it is not clear if the limitation is merely reciting an intended use of the genetic variants, or if the limitation intends to further limit one of the steps of claim 1 relating to determining a differential diagnosis, and thus require actually using the genetic variants to generate the probabilistic diagnosis. Clarification is requested. For purpose of examination, claim the limitation is interpreted to recite an intended use of the genetic variants.
Claim 16 is indefinite for recitation of “…wherein the available treatments of step (g) are utilized to generate a probabilistic diagnosis”. For the same reasons discussed above for claim 10, it is not clear if the limitation is merely reciting an intended use of the available treatments, or if the limitation intends to further limit one of the steps of claims 1 or 15 and actually require actually utilizing the available treatments to generate the probabilistic diagnosis. Clarification is requested. For purpose of examination, claim the limitation is interpreted to recite an intended use of the available treatments.
Claims 20-21 are indefinite for recitation of “The method of claim 1, wherein genetic sequencing is performed for both biological parents, and only results in which trio diplotypes fit…are obtained” and “The method of claim 20, wherein genetic sequencing is performed for both biological parents of the subject, wherein parental health status…is used to obtain only results in which parental diplotypes fit…”. Claim 1, from which claims 20-21 depends, recites “performing genetic sequencing of a DNA sample from the subject; e) determining genetic variants of the DNA; f) analyzing the results of (c) and (e);…h) analyzing the results of (f) and (g)…; generating a report comprising results of any of (a)-(h)”. First, it is unclear what results of claim 1, claims 20-21 intend to only include “…trio diplotypes [that] fit a known inheritance pattern” or “…parental diplotypes [that] fit a known inheritance pattern” (e.g. the determined variants, the results of f), the results of h)?). Furthermore, because claims 20 recites “wherein genetic sequencing is performed…” and claim 21 is grammatically unclear (e.g. ‘wherein further comprising performing…is performed..”, it is further unclear if claims 20-21 require that the method further comprises performing sequencing for both biological parents of the subject, or if the wherein clause is simply describing the process in which the “results” were previously obtained such that the genetic variant results, results of (f), results of (h), or results of any (a)-(h) are required to be determined using sequencing data of both parents. Clarification of requested. For purpose of examination, claims 20-21 are interpreted to mean any of the results of claim 1 are obtained using trio/parental diplotypes fitting a known inheritance pattern determined using genetic sequencing, but the claims do not require an active step of sequencing for both parents. If Applicant intends for claims 20-21 to require an additional method step of sequencing a DNA sample from both biological parents of the subject, claim 20 can be amended to recite “The method of claim 20, further comprising performing genetic sequencing on samples from both biological parents of the subject…”.
Claim 21, and claims dependent therefrom, are indefinite for recitation of “…wherein parental health status (healthy or affected) is used…”. The phrase "(healthy or affected)” renders the claim indefinite because it is unclear whether the phrase is part of the claimed invention, or if the claims encompass any health status. See MPEP § 2173.05(d). For purpose of examination, the phrase is interpreted to not be required by the claim, and instead is considered exemplary or optional.
Claim 28 is indefinite for recitation of “the potential differential diagnoses”. Claim 1, from which claim 28 depends, recites “a first list of potential differential diagnoses”, “a second list of potential differential diagnoses” and “a third list of potential differential diagnoses” and therefore, it is not clear which potential differential diagnoses claim 28 is referring to, or if claim 28 intends to refer to the potential differential diagnoses for each of the first, second, and third lists. Clarification is requested. For purpose of examination, claim 28 is interpreted to refer to any one or more of the potential differential diagnoses.
Response to Arguments
Applicant's arguments filed 27 May 2026 regarding 35 U.S.C. 112(b) have been fully considered but they are not persuasive.
Applicant remarks claim 1 has been amended to recite “together with the available treatments” in step h), thereby establishing antecedent basis and clarifying the treatments in h) are the same as in g), thereby resolving ambiguity (Applicant’s remarks at pg. 12, para. 2).
This argument is not persuasive. The rejection of claim 1 regarding available treatments was not regarding a lack of antecedent basis. Rather, the use of the term “available” in available treatments is a relative term that renders the claim indefinite for the reasons discussed in the above rejection.
Applicant remarks claim 8 is amended to delete “all known” (Applicant’s remarks at pg. 12, para. 3).
This argument is not persuasive. Claim 8 is not amended with the status indicator of “(Previously Presented)” and still recites “all known”. Therefore, the rejection is maintained.
Applicant remarks that claim 10 is amended to positively require the annotation and classification step (Applicant’s remarks at pg. 12, para. 4).
This argument is not persuasive because claim 10 is not amended.
Applicant remarks claim 16 is amended to recite “wherein the available treatments of step (g) are ranked…”, which positively recites the step of ranking rather than reciting an intended use (Applicant’s remarks at pg. 13, para. 1).
This argument is not persuasive. Claim 16 recites “…wherein the available treatments of step (g) are utilized to generate a probabilistic diagnostic ranked…”, which is not an active step and instead is recited passively. As a result the claim is still unclear. If Applicant intends to recite an active step, the clam can be amended to recite “The method of claim 15, further comprising utilizing the available treatments of step (g) to generate….”.
Applicant remarks claim 21 is amended to recite “further comprising performing genetic sequencing…” to clarify this is an active step (Applicant’s remarks at pg. 12, para. 3).
This argument is not persuasive. Claim 20, where the phrase “wherein genetic sequencing is performed…” first occurs is not amended and does not clearly recite an active step of sequencing samples of both parents for the reasons maintained above. Furthermore, the amendment to claim 21 is grammatically unclear and still includes a wherein clause with passive voice, “wherein further comprising performing…is performed…”, such that it is still not clear claim 21 intends to recite an active step.
Applicant remarks that “(healthy or affected)” in claim 21 has been removed, which removes the ambiguity (Applicant’s remarks at pg. 13, para. 4).
This argument is not persuasive because the claim still recites “(healthy or affected)”.
Claim Rejections - 35 USC § 112(d)
The rejection of claims 6 and 35-36 under 35 U.S.C. 112(d) in the Office action mailed 30 Dec. 2025 has been withdrawn in view of claim amendments and cancellations received 27 May 2026.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 10 and 16 are rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. This rejection is previously recited.
Claim 10 recites “…wherein the genetic variants are utilized to generate a probabilistic diagnosis and/or are annotated and classified…”, and thus only requires the limitation of “wherein the genetic variants are utilized to generate a probabilistic diagnosis” under the broadest reasonable interpretation of the claim. As discussed above, under 35 U.S.C. 112(b), the limitation is interpreted as an intended use of the genetic variants. However, claim 10 does not actually require utilizing the variants to generate a probabilistic diagnosis. As a result, claim 10 fails to further limit the subject matter of claim 9, from which it depends, under the broadest reasonable interpretation of the claim.
Claim 16 recites “wherein the available treatments of step (g) are utilized to generate a probabilistic diagnosis ranked…”, which merely recites an intended result of the available treatments and thus are not given patentable weight, as discussed above under 35 U.S.C. 112(b). Therefore, claim 16 fails to further limit the subject matter of claim 16, from which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Response to Arguments
Applicant's arguments filed 27 May 2026 regarding 35 U.S.C. 112(b) have been fully considered but they are not persuasive.
Applicant remarks that claim 10 has been amended to positively recite an annotation and classification step (Applicant’s remarks at pg. 15, para. 2).
This argument is not persuasive because claim 10 is not amended.
Applicant remarks claim 16 is amended to positively require an active ranking step (Applicant’s remarks at pg. 15, para. 3 to pg. 16, para. 1).
This argument is not persuasive because claim 16 does not recite an active ranking step for the reasons discussed above under 35 U.S.C. 112(b).
Claim Rejections - 35 USC § 101
The rejection of claims 7, 27, and 36 under 35 U.S.C. 101 in the Office action mailed 30 Dec. 2025 has been withdrawn in view of the cancellation of these claims received 27 May 2026.
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 1-6, 8-26, and 28-35 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. Any newly recited portion is necessitated by claim amendment.
The Supreme Court has established a two-step framework for this analysis, wherein a claim does not satisfy § 101 if (1) it is “directed to” a patent-ineligible concept, i.e., a law of nature, natural phenomenon, or abstract idea, and (2), if so, the particular elements of the claim, considered “both individually and as an ordered combination,” do not add enough to “transform the nature of the claim into a patent-eligible application.” Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (quoting Alice, 134 S. Ct. at 2355). Applicant is also directed to MPEP 2106.
Step 1: The instantly claimed invention (claim 1 being representative) is directed to a method. Therefore, the instantly claimed invention falls into one of the four statutory categories. [Step 1: YES]
Step 2A: First it is determined in Prong One whether a claim recites a judicial exception, and if so, then it is determined in in Prong Two if the recited judicial exception is integrated into a practical application of that exception.
Step 2A, Prong 1: Under the MPEP § 2106.04, the Step 2A (Prong 1) analysis requires determining whether a claim recites an abstract idea, law of nature, or natural phenomenon.
Claim 1 recites the following steps which fall under the mental processes groupings of abstract ideas:
(a) determining a phenome of a subject from an electronic medical record (EMR), wherein the phenome comprises a plurality of clinical phenotypes extracted from the EMR;
(b) translating the clinical phenotypes into a standardized vocabulary;
c) generating a first list of potential differential diagnoses of the subject, the first list optionally being rank ordered;
e) determining genetic variants of the DNA; f) analyzing the results of (c) and (e) to generate a second list of potential differential diagnoses of the subject, the second list being rank ordered;
g) determining the efficacy and/or quality of evidence of efficacy of available treatments for the second list of potential differential diagnoses;
h) analyzing the results of (f) and (g) to generate a third list of potential differential diagnoses of the subject by integrating the efficacy and quality of evidence of efficacy of the available treatments determined in step (g) with the second list of potential differential diagnoses, the third list being rank ordered, together with available treatments;
i) generating a report comprising results of any of (a)-(h); and
j) generating a therapy regimen based on the third list of potential differential diagnoses for the subject.
The identified claim limitations falls into the groups of abstract ideas of mental processes for the following reasons. In this case, step (a) can be practically performed in the mind by reading an EMR of the subject and determining clinical phenotypes associated with the subject. Step (b) translating encompasses simply analyzing the clinical phenotypes and converting the names for each phenotype to a consistent nomenclature, which amounts to a mere analysis of data. Generating a list of potential differential diagnoses (c) can be practically performed in the mind by organizing and writing the clinical phenotypes of the subject into a list. The step of determining genetic variants of the DNA is broadly recited and encompasses comparing sequences of the subject to a reference to identify differences, similar to the claims to "comparing BRCA sequences and determining the existence of alterations," where the claims cover any way of comparing BRCA sequences such that the comparison steps can practically be performed in the human mind, University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 763, 113 USPQ2d 1241, 1246 (Fed. Cir. 2014). Analyzing the first list and the generated variants to generate a second ranked list of differential diagnoses can be practically performed in the mind by identifying differential diagnoses of the first list that are associated with pathogenic variants, and ranking the diagnoses based on the subject having a pathogenic variant. Determining efficacy of available treatments for the second ranked list encompasses analyzing treatments for each diagnosis in the list and reading published information to determine how well each treatment works, which is a mental process. Similar to step f), analyzing the results of the second ranked list and the determined efficacy to determine a third ranked list of differential diagnoses with available treatments encompasses identifying diagnoses with an available treatment and ordering the treatments based on the efficacy of the treatment in the list. Generating a report comprising results of any of (a)-(h) can be practically performed in the mind aided by pen and paper by simply organizing the information of any of steps (a)-(h). Last, generating a therapy regimen based on the third list can be practically performed in the mind by determining a dosing frequency of an available treatment associated with the third list, which is a mere analysis of information. Overall, claim 1 recites an abstract idea analogous to "collecting information, analyzing it, and displaying certain results of the collection and analysis," where the data analysis steps are recited at a high level of generality such that they could practically be performed in the human mind, Electric Power Group v. Alstom, S.A., 830 F.3d 1350, 1353-54, 119 USPQ2d 1739, 1741-42 (Fed. Cir. 2016).
Dependent claims 2, 4, 8-9, 11-15, 17-25, 27-28, 30-32, and 34 further recite an abstract idea and/or further limit the abstract idea of claim 1 above. Dependent claim 2 further recites the mental process and certain method of organizing human activity of generating the EMR for the subject prior to (a), which involves organizing information into a record, similar to the actions a physician would carry out on a patient. Dependent claim 4 further limits the mental process of (a)-(c) and (d) and (e) to be performed simultaneously (e.g. mentally by two different people). Dependent claim 8 further limits the mental process of generating the first, second and/or third ranked list to be by querying (e.g. reading) a database. Dependent claim 9 further recites the mental process of annotating and classifying pathogenicity of variants. Dependent claim 11 further limits the mental process of analyzing variants to only retain certain variants. Dependent claim 12 further recites the mental process of annotating variants to identify and rank diplotypes based on pathogenicity. Dependent claim 13 further limits the mental process of determining the second list to comprise performing data comparisons. Dependent claim 14 further limits the mental process of determining variants to determine ranked variants. Dependent claims 15 and 17 further recites the mental process of annotating and classifying treatments into particular categories. Dependent claim 18 further limits the mental process of generating the third list to comprise performing data comparisons. Dependent claim 19 further recites the mental process of j) determining the availability of confirmatory tests for the third list, and under the broadest reasonable interpretation of the claim, none of the other limitations of the claim are required. Dependent claims 20-21 further limits the mental process of determining variants to only obtain certain results fitting a known inheritance pattern determined by parental sequencing. Dependent claim 22 further limits the mental process of determining a diagnosis of claim 1 to only use variants in the subject’s genome, but not the parental genome. Dependent claims 23-24 further limits the mental process of claim 1 to be performed on information for a particular subject. Dependent claims 25 and 28 further limit the mental process of determining a diagnosis to determine a genetic diagnosis or cancer diagnosis. Dependent claims 27 further recites the mental process of generating a therapy regime for the subject. Dependent claim 30 further recites the mental process of analyzing supplemental clinical information to determine the phenome. Dependent claims 30-31 further limit the mental process of (a) to be performed for multiple subjects. Dependent claim 34 further recites the mental process of using a database to screen for information. Therefore, claims 1-6, 8-26, and 28-35 recite an abstract idea. [Step 2A, Prong 1: YES]
Step 2A: Prong 2: Under the MPEP § 2106.04, the Step 2A, Prong 2 analysis requires identifying whether there are any additional elements recited in the claim beyond the judicial exception(s), and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. This judicial exception is not integrated into a practical application for the following reasons.
Dependent claims 2, 4, 8-9, 11-15, 17-25, 28, 30-32, and 34 recite an abstract idea, but do not recite elements in addition to the judicial exception. Dependent claims 10 and 16 fail to further limit the subject matter of claim 1, from which they depend, and are part of the abstract idea of claim 1.
The additional elements of claims 1 and 5-6 include:
d) performing genetic sequencing of a DNA sample from the subject;
wherein [the] genetic sequencing comprises, genome sequencing, rapid whole genome sequencing (rWGS), ultra-rapid whole genome sequencing, exome sequencing, or rapid whole exome sequencing (rWES) (claim 5); and
the DNA sample is from a biological sample, wherein the [biological] sample is blood, dried blood spot, serum, saliva, buccal smear/swab, plasma, feces, cerebrospinal fluid or urine (claims 6).
The additional elements of performing genome sequencing on a blood, serum, or saliva, etc. sample of a subject only serves to collect data for use by the abstract idea, which does not integrate the recited judicial exception into a practical application. See MPEP 2106.05(g).
The additional element of claims 26 and 33 include:
wherein the method is automated (claim 26);
storing on a non-transitory memory the plurality of EMRs, the plurality of phenomes, and the plurality of clinical phenotypes to generate a searchable database (claim 33).
The additional element of claim 3 includes:
wherein (b) utilizes natural language processing to perform the translation.
The additional elements of a processor for automating the method, a non-transitory memory, and storing information are generic computer components and/or processes. The courts have found the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not integrate a judicial exception into a practical application. See MPEP 2106.05(f). Further regarding “utilizing natural language processing” to perform (b), this limitation amounts to mere instructions to apply the translating step (b) on a computer (see MPEP 2106.05(f), and furthermore, merely indicates a technological field (i.e. NLP) in which to apply the abstract idea, which cannot integrate the judicial exception into a practical application.
The additional element of claims 1 and 29 further include:
administering a therapy to the subject based on the therapy regimen; and
wherein the therapy is selected from the group consisting of surgery, adjuvant chemotherapy, neoadjuvant chemotherapy, radiation therapy, hormone therapy, cytotoxic therapy, immunotherapy, adoptive T cell therapy, targeted therapy, or any combinations thereof.
The additional element of administering a therapy to the subject does not integrate the recited judicial exception into a practical application for the following reasons. MPEP 2106.04(d)(2) states the treatment or prophylaxis limitation must be "particular," i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). consider a claim that recites the same abstract idea and "administering a suitable medication to a patient." This administration step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Thus, the administration step does not integrate the mental analysis step into a practical application. In the instant case, claim 1 includes administering any therapy to the subject based on the therapy regimen according to “the third list of potential…diagnoses”, which is analogous to administering a suitable medication to the patient and does not provide integration.
While claim 29 does specify the therapy is from one of the recited groups, MPEP 2106.04(d)(2) further explains the treatment or prophylaxis limitation must have more than a nominal or insignificant relationship to the exception(s). Examiners may find it helpful to evaluate other considerations such as the insignificant extra-solution activity consideration (see MPEP § 2106.05(g)), and the field of use and technological environment consideration (see MPEP § 2106.05(h)), when making a determination of whether a treatment or prophylaxis limitation has more than a nominal or insignificant relationship to the exception(s). Here, claim 29 encompasses administering any of the recited treatments, such as a surgery, to a subject based generally on “potential differential diagnoses”. However, the recited treatments do not have any significant relationship to the judicial exception, and instead generally links the abstract idea to a particular technological environment (e.g. chemotherapy, radiation, targeted therapy etc.).
Therefore, the additionally recited elements amount to insignificant extra-solution activity, mere instructions to apply the exception, and/or generally link the abstract idea to a technological environment, and, as such, the claims as a whole do no integrate the abstract idea into practical application. Thus, claims 1-6, 8-26, and 28-35 are directed to an abstract idea. [Step 2A, Prong 2: NO]
Step 2B: In the second step it is determined whether the claimed subject matter includes additional elements that amount to significantly more than the judicial exception. See MPEP § 2106.05.
The claims do not include any additional steps appended to the judicial exception that are sufficient to amount to significantly more than the judicial exception.
Therefore, the additional element is not sufficient to amount to significantly more than the judicial exception.
Dependent claims 2, 4, 8-9, 11-15, 17-25, 28, 30-32, and 34 recite an abstract idea, but do not recite elements in addition to the judicial exception. Dependent claims 10 and 16 fail to further limit the subject matter of claim 1, from which they depend, and are part of the abstract idea of claim 1.
The additional elements of claims 1 and 5-6 include:
d) performing genetic sequencing of a DNA sample from the subject;
wherein [the] genetic sequencing comprises, genome sequencing, rapid whole genome sequencing (rWGS), ultra-rapid whole genome sequencing, exome sequencing, or rapid whole exome sequencing (rWES) (claim 5); and
the DNA sample is from a biological sample, wherein the [biological] sample is blood, dried blood spot, serum, saliva, buccal smear/swab, plasma, feces, cerebrospinal fluid or urine (claims 6).
Performing genome sequencing on a biological sample, such as a blood sample, of a subject is well-understood, routine, and conventional. This position is supported by Applicant’s own specification at para. [0080]-[0081], which explains that sequencing may be performed by any method known in the art, including shotgun sequencing (i.e. genome sequencing), massively parallel sequencing, whole genome sequencing, etc., and discloses a plurality of commercially available platforms for performing the sequencing. Applicant’s specification at para. [0129] also explains that conventional clinical genome sequencing requires preparatory steps of purifying DNA from blood of a patient, demonstrating the conventionality of sequencing DNA in a blood sample. Applicant’s specification at para. [0131] discloses commercially available software for analyzing sequencing data, further demonstrating the conventionality of sequencing with computer components.
The additional element of claims 26 and 33 include:
wherein the method is automated (claim 26);
storing on a non-transitory memory the plurality of EMRs, the plurality of phenomes, and the plurality of clinical phenotypes to generate a searchable database (claim 33).
The additional element of claim 3 includes:
wherein (b) utilizes natural language processing to perform the translation.
The additional elements of a processor for automating the method, a non-transitory memory, and storing information are generic computer components and/or processes. The courts have found the use of a computer or other machinery in its ordinary capacity for economic or other tasks (e.g., to receive, store, or transmit data) or simply adding a general purpose computer or computer components after the fact to an abstract idea (e.g., a fundamental economic practice or mathematical equation) does not provide significantly more. See Affinity Labs v. DirecTV, 838 F.3d 1253, 1262, 120 USPQ2d 1201, 1207 (Fed. Cir. 2016) (cellular telephone); TLI Communications LLC v. AV Auto, LLC, 823 F.3d 607, 613, 118 USPQ2d 1744, 1748 (Fed. Cir. 2016) (computer server and telephone unit). Further regarding performing (b) using NLP, as explained by the Supreme Court, a claim directed to a judicial exception cannot be made eligible "simply by having the applicant acquiesce to limiting the reach of the patent for the formula to a particular technological use." Diamond v. Diehr, 450 U.S. 175, 192 n.14, 209 USPQ 1, 10 n. 14 (1981). Thus, limitations that amount to merely indicating a field of use or technological environment in which to apply a judicial exception do not amount to significantly more than the exception itself. See MPEP 2106.05(h).
The additional element of claims 1 and 29 include:
administering a therapy to the subject based on the therapy regimen; and
wherein the therapy is selected from the group consisting of surgery, adjuvant chemotherapy, neoadjuvant chemotherapy, radiation therapy, hormone therapy, cytotoxic therapy, immunotherapy, adoptive T cell therapy, targeted therapy, or any combinations thereof.
Administering a therapy such as chemotherapy to a subject is well-understood, routine, and conventional. This position is supported by Applicant’s specification which generally discloses at para. [0077] that there are many available treatments for cancer, and any appropriate cancer treatment can be administered, providing examples of chemotherapy, radiation therapy, etc.
Taken alone, the additional elements do not amount to significantly more than the above-identified judicial exception(s). Even when viewed as a combination, the additional elements fail to transform the exception into a patent-eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception itself. [Step 2B: NO]
Therefore, the instantly rejected claims are not drawn to eligible subject matter as they are directed to an abstract idea (and/or natural correlation) without significantly more. For additional guidance, applicant is directed generally to applicant is directed generally to the MPEP § 2106.
Response to Arguments
Applicant's arguments filed 27 May 2026 regarding 35 U.S.C. 101 have been fully considered but they are not persuasive.
Applicant remarks that claim 1 is amended to recite “administering a therapy to the subject” which requires the actual use of the therapy on the subject and not merely prescribing or providing it, and therefore, the claims provide a practical application of treating a disease (Applicant’s remarks at pg. 16, para. 6 to pg. 17, para. 2). Applicant remarks claim 1 recites a complete clinical workflow that results in a real therapeutic outcomes, describing a case in which biotin and thiamin supplements were initiated within 3 hours of diagnosis and the patient responded, and further remarks the specification further describes various cancer treatments may be administered (Applicant’s remarks at pg. 17, para. 3 to pg. 18, para. 1).
This argument is not persuasive. While claim 1 does actively recite a treatment step, MPEP 2106.04(d)(2) states the treatment or prophylaxis limitation must be "particular," i.e., specifically identified so that it does not encompass all applications of the judicial exception(s). consider a claim that recites the same abstract idea and "administering a suitable medication to a patient." This administration step is not particular, and is instead merely instructions to "apply" the exception in a generic way. Thus, the administration step does not integrate the mental analysis step into a practical application. In the instant case, claim 1 includes administering any therapy to the subject based on the therapy regimen according to “the third list of potential…diagnoses”, which is analogous to administering a suitable medication to the patient and does not provide integration.
Regarding the example treatments for a disease recited in the specification, it is improper to import claim limitations from the specification into the claims. See MPEP 2111.01 II. In the instant case, claim 1 does not require a particular treatment for a disease.
While claim 29 does recite the therapy is one of the recited cancer treatments, this limitation is not sufficient to integrate the recited judicial exception into a practical application for the reasons discussed in the above rejection. Specifically, claim 29 encompasses administering any of the recited treatments, such as a surgery, to a subject based generally on “potential differential diagnoses”. However, the recited treatments do not have any significant relationship to the judicial exception, and instead generally links the abstract idea to a particular technological environment (e.g. chemotherapy, radiation, targeted therapy etc.).
Applicant remarks the administering step of claim 1 provides significantly more under step 2B because the claim does not merely collect, analyze, and display information, but it requires the analysis culminate in a therapeutic intervention (Applicant’s remarks at pg. 18, para. 2).
This argument is not persuasive. Under Step 2B, only the additional elements are evaluated for conventionality. The analysis of information culminating in the determined treatment is not analyzed under Step 2B given these limitations are part of the abstract idea. Furthermore, simply administering a therapy to the subject is well-understood, routine, and conventional, as discussed in the above rejection, and therefore, this additional element is not sufficient to provide significantly more.
Claim Rejections - 35 USC § 102
The rejection of claim 36 under 35 U.S.C. 102(a)(1) in the Office action mailed 30 Dec. 2025 has been withdrawn in view of the cancellation of this claim received 27 May 2026.
Claim Rejections - 35 USC § 103
The rejection of claims 7 and 27 under 35 U.S.C. 103 in the Office action mailed 30 Dec. 2025 has been withdrawn in view of the cancellation of this claim received 27 May 2026.
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 (i.e., changing from AIA to pre-AIA ) 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 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.
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.
Claims 1-6, 8-26, and 28-35 are rejected under 35 U.S.C. 103 as being unpatentable over Kingsmore (2019) in view of Schmidt (2012). Any newly recited portion is necessitated by claim amendment.
Cited references:
Kingsmore et al. US 2019/0325988 A1 (cited on IDS filed 17 Jan. 2023; previously cited); and
Schmidt et al. US 2012/0232930 A1; previously cited
Regarding claim 1, Kingsmore discloses a method comprising the following steps (Abstract; claim 1)
Kingsmore discloses a) determining a phenome of a subject from an electronic medical record (EMR), wherein the phenome comprises a plurality of clinical phenotypes extracted from the EMR (claim 1; [0007]).
Kingsmore discloses b) translating the clinical phenotypes into standardized vocabulary; (claim 1; [0008]).
Kingsmore discloses c) generating a first list of potential differential diagnoses of the subject ([0009]; claim 1).
Kingsmore discloses d) performing genetic sequencing of a DNA sample from the subject (claim1; [0010]).
Kingsmore discloses e) determining genetic variants of the DNA (claim 1; [0011]).
Kingsmore discloses f) analyzing the results of (c) and (e) to generate a second list of potential differential diagnoses of the subject, the second list being rank ordered (claim 1; [0012]).
Kingsmore discloses (g) determining or identifying a disease status comprising easing the efficacy of one or more treatment programs of a disease ([0076])
Kingsmore discloses i) generating a report comprising results of the analysis of (f) (claim 1; [0013]).
Kingsmore discloses j) generating a therapy regimen for the subject based on (g), the report of the second list of potential differential diagnoses (claims 1 and 28).
Further regarding claims 1 and dependent claims 15-17, 19, 28, and 35, Kingsmore does not disclose the following:
Regarding claim 1, Kingsmore does not disclose h) analyzing the results of (f) and (g) to generate a third list of potential differential diagnoses of the subject by integrating the efficacy and quality of evidence of efficacy of the available treatments determined in (g) with the second list of potential diagnoses, the third list being rank ordered, together with the available treatments. Kingsmore further does not disclose the therapy regimen is based on the third list in j), and k) administering a therapy to the subject based on the therapy regimen.
Regarding claims 15-17, Kingsmore does not disclose (h) further comprises annotating and classifying the available treatments, wherein the available treatments are annotated and classified as being safe and effective (SE). It is noted claim 16 fails to further limit the subject matter of claim 15, from which it depends for the reasons discussed under 35 U.S.C. 112(d), and therefore, claim 16 is addressed with claim 15 below.
Regarding claim 19, Kingsmore does not disclose j) determining the availability of confirmatory tests for the third list of potential differential diagnoses.
Regarding claim 28, Kingsmore does not disclose the potential differential diagnoses comprise cancer.
Regarding claim 35, Kingsmore does not disclose adjusting, by a user, one or more of (a)-(i) to dynamically determine available diagnoses and available treatments based on the available diagnoses for the subject.
However, Kingsmore does disclose determining or identifying a disease status comprising easing the efficacy of one or more treatment programs of a disease ([0076]) and further discloses the evidence supporting a diagnoses was manually evaluated by an expert, and if rWGS or rWES established a provisional diagnoses (i.e. a diagnosis of the second list) for which a specific treatment was available, this was immediately conveyed to the clinical team ([0085]). This demonstrates extracting a diagnosis with an available treatment from the second list.
Furthermore, regarding claim 1, Schmidt discloses a clinical decision support system for analyzing electronic health records of patient to provide differential diagnoses for a patient in addition to available therapies (Abstract; FIG. 3). Schmidt discloses generating and displaying a ranked list of differential diagnoses together with available therapy options ranked by a probability of success (i.e. analyzing (f) and (g) to generate a third rank ordered list together with available treatments by integrating the efficacy of the available treatments with the second list, and a treatment from the third list is used) ([0042]; FIG. 3, e.g. diagnoses #32, ranked by probability #25 together with therapy options #34). Schmidt further discloses a database storing data patients currently being treated ([0061]) and that users of the method may by physicians treating patients ([0062]), demonstrating a selected therapy is administered to the patient.
Regarding claims 15-17, Schmidt further discloses generating the list of differential diagnoses with available therapy options comprises annotating each available treatment with additional diagnostics and classifying each treatment with a probability of success (FIG. 3, #29 probabilities and “Rd”, “Pr”, etc. annotations under each treatment; [0045]). Schmidt discloses the treatments are annotated based on a quality of life of the patient (i.e. safe for the patient/ lower adverse events) and survival time (i.e. effectiveness), with higher probabilities of success of a therapy indicating higher quality measures of higher quality of life and higher effectiveness ([0059]).
Regarding claim 19, Schmidt further discloses further determining recommended diagnostics with each therapy option in order to refine the current diagnosis (i.e. determining availability of confirmatory tests) ([0045]; [0054] Fig. 3)).
Regarding claim 28, Schmidt further discloses the differential diagnoses include cancer (Fig. 3; [0042]; [0052]; [0054]).
Regarding claim 35, Schmidt further disclose information about diagnoses and therapies are updated (i.e. adjusted) by a user, and the past diagnoses and therapies are used to inform future diagnoses and therapy (i.e. determine available diagnoses and available treatments based on adjusting differential diagnoses) ([0024]; FIG. 8, e.g. see timeline with updates by date; FIG. 9, e.g. therapy and diagnoses history informs diagnosis and therapy next steps; [0039], e.g. recorded patient history contributes to available actions and decisions points, and success or failure of each diagnosis and therapy in the past enables the system to repeat or prevent such routes).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of Kingsmore, to have further generated a third ranked differential diagnoses list by integrating the efficacy of available treatments determined in step (g) with the second list, including cancer, together with the annotated and classified available treatments, determined available confirmatory tests for the list, administered a therapy to the subject, and adjusted the differential diagnoses history of the subject to dynamically determine new treatments and diagnoses, as shown by Schmidt above, thus arriving at the inventions of claims 1, 15-17, 19, 28, and 35. One of ordinary skill in the art would have been motivated to combine the methods of Kingsmore and Schmidt in order to assist a physician in determining the optimal sequence of clinical actions from diagnosis to therapy for cancer, in addition to enabling the system to repeat or prevent successful or failed therapies, as shown by Schmidt ([0030]; [0039]). This modification would have had a reasonable expectation of success given both Kingsmore and Schmidt analyze data to determine a list of differential diagnoses of a subject, Kingsmore discloses analyzing available treatments of the diagnoses of the second list, and thus the information and display of Schmidt is applicable to the method of Kingsmore.
Regarding the dependent claims:
Regarding claim 2, Kingsmore discloses generating the EMR for the subject prior to (a) (claim 2).
Regarding claim 3, Kingsmore discloses (b) utilizes natural language processing to perform the translation (claim 3).
Regarding claim 4, Kingsmore discloses (a)-(c) and (d)-(e) are performed in parallel (claim 4).
Regarding claim 5, Kingsmore discloses genetic sequencing comprises rapid whole genome sequencing (rWGS), ultra-rapid whole genome sequencing, or rapid whole exome sequencing (rWES) (claim 5);
Regarding claim 6, Kingsmore discloses the DNA sample is from a biological sample (claim 6), wherein the sample is serum, saliva, buccal smear/swab, plasma, feces, cerebrospinal fluid or urine (claim 7).
Regarding claim 8, Kingsmore discloses the second ranked list is performed (generated) via query of a database populated with known clinical phenotypes expressed in the same vocabulary as the standardized vocabulary of (b) (claim 11).
Regarding claim 9, Kingsmore discloses determining genetic variants of (f) further comprises annotation and classification of the genetic variants (claim 12).
Regarding claim 10, Kingsmore discloses the genetic variants are utilized to generate a probabilistic diagnosis (claim 13) and further discloses the genetic variants are annotated and classified as being of uncertain significance (VUS), pathogenic (P) or likely pathogenic (LP) (claim 14).
Regarding claim 11, Kingsmore discloses only genetic variants with an allele frequency of <5%, 2.5%, 1%, 0.1% or less in a population of healthy individuals is retained (claim 15).
Regarding claim 12, Kingsmore discloses the determining genetic variants of (e) further comprises annotation of the genetic variants to identify and rank all diplotypes as being of uncertain significance (VUS), pathogenic (P) or likely pathogenic (LP) on the basis of pathogenicity (claim 16).
Regarding claim 13, Kingsmore discloses the second list of potential differential diagnoses is generated by comparing the annotated VUS, LP and P diplotypes on a regional genomic basis with corresponding genomic regions associated with the first list of potential differential diagnoses of (c) (claim 17).
Regarding claim 14, Kingsmore discloses the genetic variants are ranked based on a combination of rank of goodness of fit of clinical phenotypes, rank of pathogenicity of diplotypes, and/or allele frequencies of the genetic variants in a population of health individuals (claim 18).
Regarding claim 18, Kingsmore further discloses determining the second list of potential differential diagnoses by comparing annotated diplotypes on a regional basis with corresponding genomic regions associated with the first list of potential differential diagnoses (claim 17; [0050]), such that the second list of potential differential diagnoses is corresponding to genomic regions associated with the first list of potential differential diagnoses. Furthermore, Kingsmore in view of Schmidt make obvious comparing this differential diagnosis list with probability information and available treatment information to generate a third ranked differential diagnoses list with available treatments, as applied above.
Regarding claim 20, Kingsmore discloses the genetic sequencing is performed for both biological parents and only results in which trio diplotypes fit a known inheritance pattern of a specific genetic disease are obtained (claim 20).
Regarding claim 21¸Kingsmore discloses the genetic sequencing is performed for both biological parents, wherein parental health status (healthy or affected) is used to obtain only results in which parental diplotypes fit a known inheritance pattern of a specific genetic disease (claim 21).
Regarding claim 22, Kingsmore discloses the genetic variants present in the subject's genome and not in the parental genome are utilized to determine a diagnosis for the subject (claim 22).
Regarding claim 23, Kingsmore discloses the subject is less than 5 years old (claim 24).
Regarding claim 24, Kingsmore discloses the subject is an infant, fetus or neonate (claim 25).
Regarding claim 25, Kingsmore discloses the potential differential diagnoses comprise genetic diseases (claim 26).
Regarding claim 26, Kingsmore discloses the method is automated (claim 27).
Regarding claim 29, Kingsmore in view of Schmidt make obvious providing a surgery or radiation therapy to the subject ([0042]; FIG. 3 of Schmidt), as applied to claims 1 and 28 above.
Regarding claim 30, Kingsmore discloses analyzing supplemental clinical information to determine the phenome (claim 30).
Regarding claim 31, Kingsmore discloses (a) is performed for a plurality of subjects thereby generating a plurality of EMRs, a plurality of phenomes, and a plurality of clinical phenotypes (claim 31).
Regarding claim 32, Kingsmore discloses (a) is performed for a plurality of subjects thereby generating a plurality of EMRs, a plurality of phenomes, and a plurality of clinical phenotypes (claim 32).
Regarding claim 33, Kingsmore discloses storing on a non-transitory memory the plurality of EMRs, the plurality of phenomes, and the plurality of clinical phenotypes to generate a searchable database (claims 33-34).
Regarding claim 34, Kingsmore discloses utilizing the database to screen for genetic data, a genotype, or a disease or disorder in a second subject or to update a diagnosis of the subject (claims 35-36).
Therefore, the invention is prima facie obvious.
Response to Arguments
Applicant's arguments filed 27 May 2026 regarding 35 U.S.C. 103 have been fully considered but they are not persuasive.
Applicant remarks that Kingsmore does not disclose generating a third list of potential differential diagnoses as claimed (Applicant’s remarks at pg. 19, para. 2-3).
This argument is not persuasive because Kingsmore is not relied upon for disclosing generating the third list. Instead, Schmidt is relied upon for this limitation.
Applicant remarks that Schmidt does not integrate treatment efficacy information with the differential diagnoses to generate a new ranked list of diagnoses, and that Schmidt discloses the “therapy options correspond to the diagnoses that is selected in the differential diagnosis panel” and that “each therapy option is listed along with a success value indicating the probability that the therapy option will be successful”, which describes therapy options being displayed for a selected diagnoses, and not the integration of treatment efficacy and quality of evidence of efficacy with a list of differential diagnoses to generate a third ranked list of diagnoses (Applicant’s remarks at pg. 19, para. 4 and pg. 20, para. 2).
This argument is not persuasive. Claim 1 recites “h) analyzing the results of (f) and (g) to generate a third list of potential diagnoses of the subject by integrating the efficacy and quality of evidence of efficacy of the available treatments determined in step (g) with the second list…”. First, the limitation of “integrating the efficacy and quality of evidence of efficacy of the available treatments” is interpreted to mean “integrating the efficacy and/or quality of evidence of efficacy of the available treatments”, as discussed in the 112(b) rejection above, given step (g) only required one of the efficacy or quality of evidence. Therefore, Applicant’s argument regarding Schmidt not disclosing integration of both “treatment efficacy and quality of evidence of efficacy” is not persuasive. However, it is noted that it is agreed that Schmidt does not teach integrating or determining “quality of evidence of efficacy” information, if the claims were amended to clarify this was required.
Second, as discussed in the above rejection, Kingsmore discloses generating a second list of potential differential diagnoses of the subject, the second list being rank ordered (claim 1; [0012]). Kingsmore discloses this second list is rank ordered by disease gene algorithms ([0085]).
Schmidt discloses generating a list of potential differential diagnoses integrated with available treatment information and the efficacy of those treatments (e.g. the probability of success of the treatments) ([0042]; FIG. 3, e.g. diagnoses #32, ranked by probability #25 together with therapy options #34). Accordingly, the combination of Kingsmore and Schmidt modifies the second list of Kingsmore with treatment efficacy information according to Schmidt, to provide a third ranked list of differential diagnoses together with available treatments. There is no requirement that available treatments are displayed for each differential diagnoses of the third list, and thus while Schmidt may only display the available treatments for a selected differential diagnoses, this still reads on the claim.
Applicant remarks that Schmidt discloses generating “a success value applicable to the entire path of clinical actions” and displaying “confidence levels” in para. [0056] and [0059], which relates to the probability of treatment success, and not to integrating efficacy and quality of evidence of efficacy of treatments with differential diagnoses to generate a new ranked list as claimed (Applicant’s remarks at pg. 20, para. 1).
This argument is not persuasive because the above cited paragraphs of Schmidt are not relied upon to teach the integrating limitation in claim 1. These paragraphs were used with respect to the limitations in claims 15 and 17 of simply annotating and classifying available treatments.
Applicant remarks that neither Kingsmore nor Schmidt alone or in combination disclose the “integrating…” limitation, and thus claim 1 and dependent clams 2-26 and 28-35 are allowable (Applicant’s remarks at pg. 20, para 3 to pg. 21, para. 1).
This argument is not persuasive for the reasons discussed above.
Double Patenting
The provisional rejections of claims 7, 27, and 36 under nonprovisional double patenting in the Office action mailed 30 Dec. 2025 have been withdrawn in view of the cancellation of these claims received 27 May 2026.
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).
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).
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.
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.
Claims 1-6, 8-26, and 28-35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7-9, 11, 13-22, 24-25, 27-44 of copending Application No. 16/388,614 in view of Schmidt (2012). Any newly recited portion is necessitated by claim amendment.
Cited reference: Schmidt et al. US 2012/0232930 A1; previously cited
Regarding instant claim 1, reference claim 1 discloses the limitations of instant claim 1, and administering a targeted treatment based on the diagnosis in (k), which generally discloses assessing available treatments. Reference claims 42-43 disclose administering the treatment.
Further regarding instant claims 1 and dependent instant claims 15-17, 19, 28, and 35, the reference claims do not disclose the following:
Regarding instant claim 1, the reference claims do not disclose h) analyzing the results of (f) and (g) to generate a third list of potential differential diagnoses of the subject, the third list being rank ordered, together with available treatments.
Regarding instant claims 15-17, the reference claims do disclose (f) analyzing the results of (c) and (e) to generate a third (h) further comprises annotating and classifying the available treatments, wherein the available treatments are annotated and classified as being safe and effective (SE). It is noted claim 16 fails to further limit the subject matter of claim 15, from which it depends for the reasons discussed under 35 U.S.C. 112(d), and therefore, claim 16 is addressed with claim 15 below.
Regarding instant claim 19, the reference claims do not disclose j) determining the availability of confirmatory tests for the third list of potential differential diagnoses.
Regarding instant claim 28, the reference claims do not disclose the potential differential diagnoses comprise cancer.
Regarding instant claim 35, the reference claims do not disclose adjusting, by a user, one or more of (a)-(i) to dynamically determine available diagnoses and available treatments based on the available diagnoses for the subject.
Furthermore, regarding instant claim 1, Schmidt discloses a clinical decision support system for analyzing electronic health records of patient to provide differential diagnoses for a patient in addition to available therapies (Abstract; FIG. 3). Schmidt discloses generating and displaying a ranked list of differential diagnoses together with available therapy options ranked by effectiveness (i.e. analyzing (f) and (g) to generate a third rank ordered list together with available treatments) ([0042]; FIG. 3, e.g. diagnoses #32, ranked by probability #25 together with therapy options #34).
Regarding instant claims 15-17, Schmidt further discloses generating the list of differential diagnoses with available therapy options comprises annotating each available treatment with additional diagnostics and classifying each treatment with a probability of success (FIG. 3, #29 probabilities and “Rd”, “Pr”, etc. annotations under each treatment; [0045]). Schmidt discloses the treatments are annotated based on a quality of life of the patient (i.e. safe for the patient/ lower adverse events) and survival time (i.e. effectiveness), with higher probabilities of success of a therapy indicating higher quality measures of higher quality of life and higher effectiveness ([0059]).
Regarding instant claim 19, Schmidt further discloses further determining recommended diagnostics with each therapy option in order to refine the current diagnosis (i.e. determining availability of confirmatory tests) ([0045]; [0054] Fig. 3)).
Regarding instant claim 28, Schmidt further discloses the differential diagnoses include cancer (Fig. 3; [0042]; [0052]; [0054]).
Regarding instant claims 35, Schmidt further disclose information about diagnoses and therapies are updated (i.e. adjusted) by a user, and the past diagnoses and therapies are used to inform future diagnoses and therapy (i.e. determine available diagnoses and available treatments based on adjusting differential diagnoses) ([0024]; FIG. 8, e.g. see timeline with updates by date; FIG. 9, e.g. therapy and diagnoses history informs diagnosis and therapy next steps; [0039], e.g. recorded patient history contributes to available actions and decisions points, and success or failure of each diagnosis and therapy in the past enables the system to repeat or prevent such routes).
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to have modified the method of the reference claims, to have further generated a third ranked differential diagnoses list, including cancer, together with the annotated and classified available treatments, determined, available confirmatory tests for the list, and adjusted differential diagnoses to determine available diagnoses and treatments, as shown by Schmidt above, thus arriving at the inventions of instant claims 1, 15-17, 19, 28, and 35. One of ordinary skill in the art would have been motivated to combine the methods of the reference claims and Schmidt in order to assist a physician in determining the optimal sequence of clinical actions from diagnosis to therapy for cancer, as shown by Schmidt ([0030]). This modification would have had a reasonable expectation of success given both the reference claims and Schmidt analyze data to determine a list of differential diagnoses of a subject, and thus the information and display of Schmidt is applicable to the method of the reference claims.
Reference claims 2-4 disclose the limitations of instant claims 2-4.
Reference claim 1 and 7 disclose the limitations of instant claims 5-6.
Reference claim 11 discloses the limitation of instant claim 8.
Reference claim 14-18 discloses the limitation of instant claims 9-15.
Regarding instant claim 18, reference claim 17 discloses determining the second list of potential differential diagnoses by comparing annotated diplotypes on a regional basis with corresponding genomic regions associated with the first list of potential differential diagnoses, such that the second list of potential differential diagnoses is corresponding to genomic regions associated with the first list of potential differential diagnoses. Furthermore, the reference claims in view of Schmidt make obvious comparing this differential diagnosis list with probability information and available treatment information to generate a third ranked differential diagnoses list with available treatments, as applied above.
Reference claims 20-22 disclose the limitation of instant claims 20-22.
Reference claims 24-25 disclose the limitation of instant claims 23-24
Reference claim 1 discloses the limitation of instant claim 25.
Reference claim 27-28 the limitation of instant claims 26 and 29.
Reference claims 30-34 discloses the limitation of instant claims 30-34.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant's arguments filed 27 May 2026 regarding double patenting have been fully considered but they are not persuasive because they do not present any arguments.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this 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).
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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAITLYN L MINCHELLA whose telephone number is (571)272-6485. The examiner can normally be reached 7:00 - 4:00 M-Th.
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/KAITLYN L MINCHELLA/Primary Examiner, Art Unit 1685
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