Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of Claims
Claims 1-20 were pending.
Claims 2, 3, 5-8, 10-13, 15-16, 18-19 are canceled.
Claims 1, 4, 9, 14, 17, 20 are amended.
Claims 21-24 are new.
Claims 1, 4, 9, 14, 17, 20-24 are under consideration.
Information Disclosure Statement
(new addition) The information disclosure statement (IDS) submitted on 06/02/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
(new objection) The drawings are objected to because the drawings are indicated by “Figure” rather than “FIG.” as required by 37 C.F.R § 1.84 (u)(1) (see also MPEP § 608.02 (V)). The different views must be numbered in consecutive Arabic numerals, starting with 1, independent of the numbering of the sheets and, if possible, in the order in which they appear on the drawing sheet(s). 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. View numbers must be preceded by the abbreviation “FIG.” Where only a single view is used in an application to illustrate the claimed invention, it must not be numbered and the abbreviation “FIG.” must not appear.
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.
Specification
(previous objection, withdrawn) The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The disclosure is objected to because of the following informalities: The title of the invention is correct on the specification. However, the title on the Application Data Sheet 37 CFR 1.76 has the following typo: “BOLOGICAL”. For improved language, the Title of the Invention should recite “BIOLOGICAL”. Appropriate correction is required.
Applicant contends: The Office Action objects to the title of the application as there is a typographical error in the ADS. A corrected ADS is submitted herewith to correction “BOLOGICAL” to “BIOLOGICAL” as is provided for in the specification. Withdrawal of the objection is requested.
Office response: Based on the amendment, the objection is withdrawn.
(new objection) The disclosure is objected to because of the following informalities:
(1) The drawings are indicated by “Figure” rather than “FIG.” See objection to the drawings, above.
(2) The use of the term C-SAND® (p. 5), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
(previous objection, withdrawn) Claims 2, 5, 13, 16, 20 are objected to because of the following informalities:
a. Claims 2, 5: For improved language, the claim should recite SARS-CoV-2 instead of SARS-Cov2.
b. Claim 13: For improved language, remove additional “mM” typo.
c. Claim 16: For improved language, the claim should recite “collected biological sample” instead of “collect biological sample”.
d. Claim 20: For improved language, the claim should recite “isothiocyanate” instead of “isothicynate”.
Appropriate correction is required.
Applicant contends: The Office Action objects to claim informalities regarding various typographical and grammatical errors. The claims have been amended to adopt the Office’s suggestions and / or cancelled and withdrawal of the objection is requested.
Office response: Claims 2, 5, 13, 16 are canceled and so their objection is moot. Based on the amendment to claim 20, its objection is withdrawn.
(new objection) Claim 1 is objected to because of the following informalities:
Claim 1: Claim 1 recites “viral transport media solution, where the nucleic acid analyzed”. Change “where” to “wherein” for consistency with other claims.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
(previous rejection, withdrawn) Claims 1-20 are rejected under 35 U.S.C. 112 (b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
See claims 1, 4, 9, 14, 17, 20 as submitted 06/02/2026.
Claims 1 and 17 are unclear as written: The preambles for both claims recite “without isolation or purification of the nucleic acids prior to detection of the nucleic acids”. Yet, the claims further recite steps (contacting, heating, analyzing) without referring to excluding the isolation or purification steps. It is unclear at which step the isolation or purification steps are excluded. For improved language and meaning, claims 1 and 17 should recite “contacting a collected biological sample with a treatment buffer without isolating or purifying nucleic acids in the sample“ to be clearer and continue to clarify for each step (heating, analyzing, etc. ) that follows.
It is also not clear how “nucleic acid analyzed” in both bodies of the claims equates to “detection of nucleic acids” as written in both preambles. Depending on the inventors’ intent, improved language could be, for example in claim 2 “nucleic acid analyzed detects the SARS-CoV-2 ribonucleic acid virus”. Similar improvements can be made in claims 5,7,10,12, and 15.
Additionally for claim 15, it is also unclear if the nucleic acid analyzed is a hemochromatosis (HFE) gene having a “G63D” mutation or “H63D” mutation, as more commonly found in the art. For instance, Collier et al. (US20100291666A1) teaches the second most prevalent mutation in the same hemochromatosis gene is a C to G transversion in exon 2, known as H63D. Leao et al. (previously cited) also teaches a second mutation, H63D (a histidine-to-aspartate substitution), resulting from a transversion C (cytosine) to G in position 187 of the HFE gene (p. 179).
Applicant contends: The Office Action provides that the preamble does not sufficiently define the negative limitation of without isolation or purification of nucleic acids prior to detection. As amended claims 1 and 17, and new claims 21 – 24 provide that without isolation or purification of nucleic acids in the sample to definitively define where isolation and purification does not occur.
The Office Action provides that it is not clear how “nucleic acid analyzed” in the bodies of the claims relates to “detection of nucleic acids” in the preambles. As amended claims 1 and 17, and new claims 21 - 24 further limit analyzing the biological sample to detecting at least one nucleic acid sequence using particular nucleic acid detection methods. This specificity directly ties the nucleic acid analysis to the detection of a nucleic acid sequence.
With respect to claim 15 (now reflected in new claim 24), the Office Action provides that it is not clear whether the mutation for detection is the “G63D” or “H63D” mutation of the hemochromatosis gene. Applicant confirms that this is the H63D mutation as is commonly found in the art, as noted by the Office, and has appropriately incorporated this into new claim 24 and the specification to correct this typographical error.
Office response: Claims 2-3, 5-8, 10-13,15-16 are canceled and so their rejection is moot. And, based on the amendments, the rejection of claims 1, 4, 9, 14, 17, 20 are withdrawn.
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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.
(previous rejection, claim canceled, rejection moot) Claim 16 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, 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
Applicant contends: The Office identifies the improper dependent form of claim 16, which is moot with the cancellation of claim 16.
Office response: With cancellation of claim 16, the rejection is moot.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
(previous rejection, withdrawn) Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
See claims 1, 4, 9, 14, 17, 20 as submitted 04/05/2023.
Applicant contends: The Office rejects claims 1 – 20 under 35 U.S.C. 101 asserting the claimed invention is directed to the judicial exception of mental processes within category of abstract ideas. Applicant disagrees as amended claims 1 and 17 and new claims 21 – 24 are patent eligible under the following step of the subject matter eligibility test.
Step 2A, Prong Two
As set forth in MPEP § 2106.05(a)(II), an improvement to the technology or technical field provides patentable subject matter under Step 2A, prong two when the improvement includes components or methods, such as techniques, that generate new data. The amended claims provide an improvement in the form of a new technique for analyzing a biological sample to detect a nucleic acid sequency without isolating or purifying nucleic acids. The use of these detection techniques via polymerase chain reaction (PCR), reverse transcriptase (RT) PCR, real-time PCR, quantitative PCR, and isothermal amplification, as required by the claim and with this limitation it is impossible to produce the analyzing in a human mind. Thus, the amended claims include a new technique of detection of nucleic acids without isolation or purification to provide a practical application of the abstract idea of mental processes to meet the requirements of Section 101.
Office response: Applicant’s arguments, see pages 3-4, filed 06/02/2026, with respect to claims 1, 17 have been fully considered and are persuasive. The rejection of claims 1, 4, 9, 14, 17, 20 has been withdrawn. Claims 2-3, 5-8, 10-13, 15-16, 18-19 are canceled and so their rejection is moot.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (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.
(previous rejection, withdrawn, claim 1 amended) Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable by Oommen (“Oommen 2018”)(US2018/0105809 A1) (previously cited).
See claim 1 as submitted 06/02/2026.
(previous rejection, withdrawn, claims 2, 5 canceled) Claims 2 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Oommen 2018 in view of Ganguli at al. (“Ganguli”)(cited in applicant’s IDS submitted 04/05/2023).
See claims 2 and 5 as submitted 06/02/2026.
(previous rejection, withdrawn, claim 3 canceled, amended claim 4 dependent on claim 1) Claims 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Oommen 2018 in view of Ganguli, and further in view of Fischer et al. (“Fischer”)(US9416416B2) (previously cited).
See claims 3 and 4 as submitted 06/02/2026.
(previous rejection, withdrawn, claim canceled) Claim 6 is rejected under 35 U.S.C 103 as being unpatentable over Oommen 2018 in view of Ganguli as applied to claim 5, and further in view of Fischer and in view of Grobler et al (“Grobler”)(20140370508) (cited in applicant’s IDS submitted 04/05/2023).
See claim 6 as submitted 06/02/2026.
(previous rejection, withdrawn, claim canceled) Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Oommen 2018 as applied to claim 1 above, in view of Plut et al. (“Plut”) (previously cited).
See Claim 7 as submitted 06/02/2026.
(previous rejection, withdrawn, claim 8 canceled, amended claim 9 dependent on new claim 21) Claims 8 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Oommen 2018 in view of Plut as applied to claim 7 above, and further in view of Fischer, and in view of Grobler, and in view of Abate et al. (“Abate”)(US9487581B2) (previously cited).
See claims 8 and 9 as submitted 06/02/2026.
(previous rejection, withdrawn, claim canceled) Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Oommen 2018 as applied to claim 1 above, in view of Plut and further in view of Jestin et al. (“Jestin”)(US20120005768 A1) (cited in applicant’s IDS submitted 04/05/2023).
See claim 10 as submitted 06/02/2026.
(previous rejection, withdrawn, claim canceled) Claims 11 is rejected under 35 U.S.C. 103 as being unpatentable over Oommen 2018 in view of Plut and Jestin as applied to claim 10 above, and further in view of Fischer and in view of Abate (previously cited).
See claim 11 as submitted 06/02/2026.
(previous rejection, withdrawn, claim canceled) Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Oommen 2018 in view of Fischer and further in view of Lopez et al. (“Lopez”)(cited in applicant’s IDS submitted 04/05/2023).
See claim 12 as submitted 06/02/2026.
(previous rejection, withdrawn, claim 13 canceled; amended claim 14 dependent on new claim 23) Claims 13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Oommen 2018, in view of Fischer and Lopez as applied to claim 12 above, and further in view of Shaw et al. (“Shaw”) (previously cited).
See claims 13 and 14 as submitted 06/02/2026.
(previous rejection, withdrawn, claims canceled) Claims 15 and 16 are rejected under 35 U.S.C. 103 as being unpatentable over Oommen 2018 in view of Fischer, and further in view of Collier et al. (“Collier”)(US20100291666A1) and Lui et al. (“Lui”)(US20200023353A1) (previously cited).
See claims 15 and 16 as submitted 06/02/2026.
(previous rejection, withdrawn, claims 18 and 19 canceled, claims 17 and 20 amended) Claims 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Oommen (2018) in view of Fischer.
See claims 17-20 as submitted 06/02/2026.
Applicant contends:
(1) Claim 1 is rejected under 35 U.S.C. 103 as being obvious in view of Oommen. As amended, claim 1 incorporates the limitations of claims 2, 3, 5, and 6, which are further rejected as obvious in view of Ganguli, Fischer, and Grobler. As stated by the Office, Oommen does not teach percentage, molarity, pH specifics of the treatment buffer comprising 10% Bovine Serum Albumin, 0.4mM ethylene diamine tetra acetic acid of pH 8, 48 mM Guanidine isothiocyanate, and 8 mM Tris(hydroxymethyl)aminomethane hydrochloride of pH 9.0 of a volume equal to the volume of collected biological sample. (Office Action pgs. 14 – 15). There is no motivation to modify Oommen as the method of Oommen includes isolation of the nucleic acids through binding of the nucleic acids (Oommen, paragraph [0031]), whereas amended claim 1 negatively limits any isolation of purification of the nucleic acids. Further, there is no likelihood of success in modifying Oommen given that the treatment buffer is in the field of unpredictable arts, as the interactions between buffer components at varying concentrations produces unpredictable results, none of which can be determined without trying an undetermined number of experiments. This would not be routine optimization as the particular buffer components, amounts, concentration, and pH are necessary for efficacy of Applicant’s claim 1, where this efficacy is demonstrated via the examples of Figs. 3 and 4 in Applicant’s specification. (MPEP § 2144.05.III.).
As further provided by the Office, Fischer does not teach the particular composition of Applicant’s treatment buffer. (Office Action pgs. 15 – 16, evidenced by the stated need of one of ordinary skill in the art to make adjustments to the components of the treatment buffer). There is no motivation in Fischer as the composition and method of Fischer includes further isolation and purification of the nucleic acids. (Fischer, Column 15, Lines 45 – 50; Abstract), and amended claim 1 negatively limits any isolation or purification of the nucleic acids. Further, there is no likelihood of success in modifying Fischer given that the treatment buffer is in the field of unpredictable arts, as the interactions between buffer components at varying concentrations produces unpredictable results, none of which can be determined without trying an undetermined number of experiments. This would not be routine optimization as the particular buffer components, amounts, concentration, and pH are necessary for efficacy of Applicant’s claim 1, where this efficacy is demonstrated via the examples of Figs. 3 and 4 in Applicant’s specification. (MPEP § 2144.05.III.).
As further provided by the Office, Grobler does not teach the particular composition of Applicant’s treatment buffer. (Office Action pg. 17, evidenced by the stated citation of Grobler is with respect to the use of sodium citrate). There is no motivation in Grobler as the composition and method of Grobler includes further isolation and purification of the nucleic acids via precipitating RNA (Grobler, paragraph [0016] with respect to U.S. Pat. No. 5,346,994) or using the capturing scaffold (Grobler [0052]), whereas amended claim 1 negatively limits any isolation or purification. Further, there is no likelihood of success in modifying Grobler given that the treatment buffer is in the field of unpredictable arts, as the interactions between buffer components at varying concentrations produces unpredictable results, none of which can be determined without trying an undetermined number of experiments. This would not be routine optimization as the particular buffer components, amounts, concentration, and pH are necessary for efficacy of Applicant’s claim 1, where this efficacy is demonstrated via the examples of Figs. 3 and 4 in Applicant’s specification. (MPEP § 2144.05.III.).
Finally, Ganglia does not teach the treatment buffer of Applicant’s amended claim 1 as stated by the office (Office Action pg. 17), nor does it teach the concentrations of .4mM ethylene diamine tetra acetic acid of pH 8, 48 mM guanidine isothiocyanate, and 8 mM Tris (hydroxymethyl)aminomethane. There is no likelihood of success in modifying Ganglia given that the treatment buffer is in the field of unpredictable arts, as the interactions between buffer components at varying concentrations produces unpredictable results, none of which can be determined without trying an undetermined number of experiments. This would not be routine optimization as the particular buffer components, amounts, concentration, and pH are necessary for efficacy of Applicant’s claim 1, where this efficacy is demonstrated via the examples of Figs. 3 and 4 in Applicant’s specification. (MPEP § 2144.05.III.). Finally, there is no result dependent variable for the treatment buffer used in a nucleic acid detection without isolation or purification of the nucleic acid as stated in amended claim 1 without undue experimentation.
As Oommen, Ganglia, Grobler, and Fischer do not teach or suggest the treatment buffer of Applicant’s claim 1, Applicant requests that rejection of Claim 1 and 4, which depends therefrom be withdrawn.
(2) Claims 7 is rejected under 35 U.S.C. 103 as being obvious in view of Oommen and further in view of Plut. Claims 8 and 9 are rejected under 35 U.S.C. 103 as being obvious in view of Oommen in further view of Fischer, Grobler, and Abate. New claim 21 incorporates the limitations of claims 7 and 8. As stated by the Office neither Oommen, Plut, Fischer, Gobler, or Abate teach the treatment buffer. (Office Action pg. 22, as evidenced by the Office’s reference to the combination of the treatment buffer components from the cited references). As discussed above, there is no motivation to modify Oommen, Fischer, and Grobler, and no predictability of success in doing so given that formulation of a treatment buffer is not routine optimization. Neither Plut or Abate include such motivation or include such likelihood of success.
There is no motivation in Plut for the treatment buffer as the composition and method of Plut includes further isolation of the nucleic acids via elution of the DNA and RNA (Plut, pg. 6), whereas new claim 21 negatively limits isolation or purification of the nucleic acids. Further, there is no likelihood of success in modifying Plut given that the treatment buffer is in the field of unpredictable arts, as the interactions between buffer components at varying concentrations produces unpredictable results, none of which can be determined without trying an undetermined number of experiments. This would not be routine optimization as the particular buffer components, amounts, concentration, and pH are necessary for efficacy of Applicant’s new claim 21, where this efficacy is demonstrated via the examples of Fig. 5 in Applicant’s specification. (MPEP § 2144.05.III.).
There is no motivation in Abate for the treatment buffer as the composition and method of Abate are directed toward the stability of certain monoclonal antibodies, not a method of direct detection of nucleic acids (Abate, Column 25, Lines 7 - 32). Further, there is no likelihood of success in modifying Abate given that the treatment buffer is in the field of unpredictable arts, as the interactions between buffer components at varying concentrations produces unpredictable results, none of which can be determined without trying an undetermined number of experiments. This would not be routine optimization as the particular buffer components, amounts, concentration, and pH are necessary for efficacy of Applicant’s new claim 21, where this efficacy is demonstrated via the examples of Fig. 5 in Applicant’s specification. (MPEP § 2144.05.III.). Finally, there is no result dependent variable for the treatment buffer used in a nucleic acid detection without isolation or purification of the nucleic acid as stated in new claim 21 without undue experimentation.
As Oommen, Grobler, Fischer, Plut, and Abate do not teach or suggest the treatment buffer of Applicant’s claim 21, Applicant requests that rejection of claim 21 and claim 9, which depends therefrom be withdrawn.
(3) Claim 10 is rejected under 35 U.S.C. 103 as being obvious in view of Oommen and further in view of Plut and Jestin. Claim 11 is rejected under 35 U.S.C. 103 as being obvious in view of Oommen in further view of Plut, Jestin, Fischer and Abate. New claim 22 incorporates the limitations of claims 10 and 11. As stated by the Office neither Oommen, Plut, Jestin, Abate, nor Fischer teach the treatment buffer. (Office Action pg. 25 and 26, as evidenced by the Office’s reference to the combination of the treatment buffer components from the cited references). As discussed above, there is no motivation to modify Oommen, Plut, Abate, and Fischer, and no predictability of success in doing so given that formulation of a treatment buffer is not routine optimization. Nor does Jestin include such motivation or likelihood of success.
There is no motivation in Jestin to the treatment buffer of Applicant’s new claim 22 as the invention of Jestin is directed toward non-naturally occurring sequences and methods of detection of such sequences, where the kits for detection of the sequences do not include instructions for amplification without purification of nucleic acids (Jestin, paragraphs [00154], [00251] – [0276]). Further, there is no likelihood of success in modifying Jestin given that the treatment buffer is in the field of unpredictable arts, as the interactions between buffer components at varying concentrations produces unpredictable results, none of which can be determined without trying an undetermined number of experiments. This would not be routine optimization as the particular buffer components, amounts, concentration, and pH are necessary for efficacy of Applicant’s new claim 22, where this efficacy is demonstrated via the example of Fig. 6 in Applicant’s specification. (MPEP § 2144.05.III.). Finally, there is no result dependent variable for the treatment buffer used in a nucleic acid detection without isolation or purification of the nucleic acid as stated in new claim 22 without undue experimentation.
As Oommen, Plut, Jestin, Fischer, and Abate do not teach or suggest the treatment buffer of Applicant’s claim 22, Applicant requests that rejection of Claim 22 be withdrawn.
(4) Claim 12 is rejected under 35 U.S.C. 103 as being obvious in view of Oommen and further in view of Fischer and Lopez. Claim 13 is rejected under 35 U.S.C. 103 as being obvious in view of Oommen in further view of Fischer, Lopez, and Shaw. New claim 23 incorporates the limitations of claims 12 and 13. As stated by the Office neither Oommen, Fischer, Lopez, nor Shaw teach the treatment buffer. (Office Action pg. 29, as evidenced by the Office’s reference to the combination of the treatment buffer components from the cited references). As discussed above, there is no motivation to modify Oommen and Fischer, and no predictability of success in doing so given that formulation of a treatment buffer is not routine optimization. Nor do Lopez or Shaw provide such motivation or likelihood of success.
There is no motivation to modify Shaw to Applicant’s treatment buffer of new claim 23, as Shaw is directed towards sample preparation methods that include purification (i.e. sample prefractionation), where Applicant’s claim 23 negatively limits any purification. (Shaw, Sections 3.1 and 4). Further, there is no likelihood of success in modifying Shaw given that the treatment buffer is in the field of unpredictable arts, as the interactions between buffer components at varying concentrations produces unpredictable results, none of which can be determined without trying an undetermined number of experiments. This would not be routine optimization as the particular buffer components, amounts, concentration, and pH are necessary for efficacy of Applicant’s new claim 23, where this efficacy is demonstrated via the example of Fig. 7 in Applicant’s specification. (MPEP § 2144.05.III.).
Further, there is no motivation to modify Lopez to Applicant’s treatment buffer of new claim 23, as Lopez is directed towards sample preparation methods that include purification (i.e. nucleic acid extraction using magnetic beads), where Applicant’s claim 23 negatively limits any purification. (Lopez, Section2.3). Further, there is no likelihood of success in modifying Lopez given that the treatment buffer is in the field of unpredictable arts, as the interactions between buffer components at varying concentrations produces unpredictable results, none of which can be determined without trying an undetermined number of experiments. This would not be routine optimization as the particular buffer components, amounts, concentration, and pH are necessary for efficacy of Applicant’s new claim 23, where this efficacy is demonstrated via the example of Fig. 7 in Applicant’s specification. (MPEP § 2144.05.III.). Finally, there is no result dependent variable for the treatment buffer used in a nucleic acid detection without isolation or purification of the nucleic acid as stated in amended claim 1 without undue experimentation.
As Oommen, Fischer, Lopez, and Shaw do not teach or suggest the treatment buffer of Applicant’s claim 23, Applicant requests that rejection of Claim 23 and 14, which depends therefrom be withdrawn.
(5) Claims 15 and 16 are rejected under 35 U.S.C. 103 as being obvious in view of Oommen and further in view of Fischer, Collier and Lui. New claim 24 incorporates the limitations of claims 15 and 16. As stated by the Office neither Oommen, Fischer, Collier, nor Lui teach the treatment buffer. (Office Action pg. 31 and 32, as evidenced by the Office’s reference to the combination of the treatment buffer components from the cited references). As discussed above, there is no motivation to modify Oommen and Fischer, and no predictability of success in doing so given that formulation of a treatment buffer is not routine optimization. Nor do Collier or Lui provide such motivation or likelihood of success.
There is no motivation to modify Collier to Applicant’s treatment buffer of new claim 24, as Collier is directed towards extraction procedures that include purification (i.e. removal of known inhibitor of the PCR reaction from genomic DNA), where Applicant’s claim 23 negatively limits any purification. (Collier, Abstract and paragraph [0049]). Further, there is no likelihood of success in modifying Collier given that the treatment buffer is in the field of unpredictable arts, as the interactions between buffer components at varying concentrations produces unpredictable results, none of which can be determined without trying an undetermined number of experiments. This would not be routine optimization as the particular buffer components, amounts, concentration, and pH are necessary for efficacy of Applicant’s new claim 24, where this efficacy is demonstrated via the example of Fig. 8 in Applicant’s specification. (MPEP § 2144.05.III.).
Further, there is no motivation to modify Lui to Applicant’s treatment buffer of new claim 24, as Lui is directed towards methods, devices, systems, and kits for the collection and analysis of samples obtained by swabs that include extraction procedures that include purification (i.e. use of extraction buffers and devices for filtration, separation, etc.), where Applicant’s claim 23 negatively limits any purification. (Lui, Abstract and paragraphs [0068] and [00123]). Further, there is no likelihood of success in modifying Lui given that the treatment buffer is in the field of unpredictable arts, as the interactions between buffer components at varying concentrations produces unpredictable results, none of which can be determined without trying an undetermined number of experiments. This would not be routine optimization as the particular buffer components, amounts, concentration, and pH are necessary for efficacy of Applicant’s new claim 24, where this efficacy is demonstrated via the example of Fig. 8 in Applicant’s specification. (MPEP § 2144.05.III.). Finally, there is no result dependent variable for the treatment buffer used in a nucleic acid detection without isolation or purification of the nucleic acid as stated in amended claim 1 without undue experimentation.
As Oommen, Fischer, Collier, and Lui do not teach or suggest the treatment buffer of Applicant’s claim 24, Applicant requests that rejection of Claim 24 be withdrawn.
(6) Claims 17 – 20 are rejected under 35 U.S.C. 103 as being unpatentable over Oommen in view of Fischer. Neither Oommen, nor Fischer teach the treatment buffer of Applicant’s amended claim 17. (Office Action, pg. 35, as evidenced by the stated need of one of ordinary skill in the art to make adjustments to the components of the treatment buffer). For the reasons stated above neither Oommen, nor Fischer provide a motivation to modify the buffers to Applicant’s treatment buffer. Further, for the reasons noted above, there is no likelihood of success in modifying the treatment buffer as the treatment buffer is in the field of unpredictable arts.
As Oommen and Fischer do not teach or suggest the treatment buffer of Applicant’s claim 17, Applicant requests that rejection of Claim 17 and 20, which depends therefrom be withdrawn.
Office response:
Applicant amended claim 1, incorporating the limitations of claims 2, 3, 5, and 6 while also addressing a 112(b) rejection above. As a result, claims 2, 3, 5, and 6 were canceled. As a result of their cancellation, the rejections of claims 2, 3, 5 and 6 are moot. As a result of the amendments to claim 1, the rejections of claims 1 and 4 are withdrawn. See new rejections as necessitated by amendment below.
Applicant amended claim 17, incorporating the limitations of claims 18, and 19. As a result, claims 18 and 19 were canceled. As a result of their cancellation, the rejections of claims 18, and 19 are moot. Claim 20, previously dependent on claim 19, is amended to depend on amended claim 17. As a result of the amendments to claims 17 and 20, the rejections of claims 17 and 20 are withdrawn. See new rejections as necessitated by amendments below.
Applicant added new claims 21, 22, 23, and 24.
New claim 21 incorporates the limitations of claims 7 and 8. As a result, claims 7 and 8 were canceled. Amended claim 9 is now dependent on claim 21. As a result of their cancellation, the rejection of claims 7 and 8 are moot. As a result of amendment to claim 9, now dependent on claim 21, and new claim 21, the rejection of claim 9 is withdrawn. See new rejections as necessitated by amendment and entry of new claim below.
New claim 22 incorporates the limitations of claim 10 and 11. As a result, claims 10 and 11 were canceled. As a result of their cancellation, the rejection of claims 10 and 11 are moot. See new rejection as necessitated by entry of new claim below.
New claim 23 incorporates the limitations of claims 12 and 13. As a result, claims 12 and 13 were canceled. As a result of their cancellation, the rejections of claims 12 and 13 are moot. Claim 14 is amended to depend on claim 23. See new rejection as necessitated by amendment and entry of new claim below.
New claim 24 incorporates the limitations of claims 15 and 16. As a result, claims 15 and 16 are canceled. As a result of their cancellation, the rejections of claims 15 and 16 are moot. See new rejection as necessitated by entry of new claim below.
Regarding the Oomen 2018 reference, while the Oomen 2018 reference does teach follow-on steps suggestive of “isolation and purification of nucleic acid”, the initial steps of combining different types of biological samples with a lysis buffer and potentially incubating it at 37-95 degrees Celsius for a period of time, such as 2 minutes to 3 hours [0048] does appear to facilitate the release of nucleic acids from cells, the so-called “free” nucleic acids [0020]. Oomen 2018 provides examples of lysis buffer in reference claim 20: the lysis buffer further comprises a substance chosen from the group consisting of lysozyme, proteinase k, and sodium hydroxide, reference claims 24: The lysis buffer is selected from the group consisting from 0.2 to 5 percent triton x-100 (volume triton x-100/volume water), from 2 to 50 millimolar aqueous trishydrochloride, and aqueous 1 millimolar ethylenediaminetetra-acetic acid having a pH from 5.5 to 7.5, and combinations thereof; as well as paragraphs [0035] and [0036].
Within the art, Liu et al. (Liu)(See PTO-892 Notice of References Cited; and see new rejection of claim 24 below) teaches sample lysis with sodium hydroxide and then direct isothermal amplification without nucleic acid purification. As a result, Oomen 2018’s teachings of treating a biological sample with a lysis buffer and potentially heating it as way to free nucleic acid could be leveraged by one of ordinary skill in the art to investigate ways to eliminate the resource intensive isolation or purification of nucleic acid steps prior to amplification and in general speed up processes.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
The “no motivation to” concerns in the argument above appear to be centered on (1) art with follow on steps that include isolation or purification of the nucleic acid or (2) on combining teachings related to buffers and their use in the treatment buffer composition. Extraction-free amplification and the need for low cost and rapid approaches to biological sampling for viral detection is explored in the art. For instance, Ganguli notes, “The fundamental limitations of current diagnostic assays for viral pathogens stem from their reliance upon PCR analysis, which requires temperature cycling as well as labor-intensive, laboratory-based protocols for viral isolation, lysis, and removal of inhibiting materials. Although, recently, the RT-qPCR technique has demonstrated detection of SARS-CoV-2, bypassing the need for RNA isolation/purification starting from a saliva sample (5), the PCR technique is not easily adaptable for point-of-use detection, due to the need for temperature cycling. While PCR remains the proven gold standard for clinical diagnostics, there is an urgent need for other approaches that are sufficiently low cost and rapid to provide diagnosis at the point of use”(p. 22727).
Regarding different lysis buffer compositions, it is true that Oomen 2018 limits the lysis buffers to the ones mentioned above. However, the end-result of using either a lysis buffer or a “treatment buffer” (as noted in the instant application) is to free up the nucleic acids.
One skilled in the art would be aware of different buffers that can be used alone or in combination for their lytic function as well as buffers with the ability to stabilize and preserve the integrity of the nucleic acid prepared from different biological samples (e.g., nasal swabs, oral fluids, porcine serum, porcine processing fluid, oral swabs) for subsequent amplification.
The applicant contends that the treatment buffer is in the field of unpredictable arts, as the interactions between buffer components at varying concentrations produces unpredictable results, none of which can be determined without trying an undetermined number of experiments. However, the buffers, their modes of action, their rationale for use, even different combinations, as well as ranges of molarity or pH are suggested, or known, in the arts as evidenced in the prior art rejections used in this action. For instance, Fischer (previously cited), for example, in reference claim 1 teaches “an aqueous mixture at a pH of about 6 to 7 that contains: a control nucleic acid sequence, one or more chaotropes; one or more detergents; one or more reducing agents; one or more chelators; and one or more buffers, collectively and in an amount sufficient to denature proteins, inactivate nucleases, kill pathogens, and release nucleic acid from an organism or cell contained within the biological sample when contacted with the biological sample in solution, wherein: upon contact with the biological sample in solution, the released nucleic acid and the control nucleic sequence acid are each detectable in solution by nucleic acid testing for at least 7 days when stored at a temperature of greater than 4° C and the control nucleic acid sequence is distinguishable from the released nucleic acid; and the control nucleic acid sequence and the released nucleic acid in solution are detectable by a single nucleic acid testing”. Fischer also suggests different ranges of molarity.
As previously mentioned in the claim rejections, absent unexpected results, optimization of parameters such as molarity, pH, volume, temperature and time is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results, such as, for example, the desired 48mM guanidine isothiocyanate. The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."(Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature or even time will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Therefore, Applicant's arguments, filed 06/02/2026, have been fully considered but they are not persuasive.
(new rejection, as necessitated by amendment) Claims 1, 4, 17, 20 are rejected under 35 U.S.C. 103 as being unpatentable over Ganguli (previously cited) in view of Grobler (previously cited), in view of Fischer (previously cited), and in view of Oomen 2018 (previously cited).
See claims 1, 4, 17, 20 as submitted 06/02/2026.
Regarding claim 1, 4, 17, and 20:
Ganguli teaches an RT-LAMP isothermal assay for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and demonstrate the assay on clinical samples using a simple and accessible point-of-care (POC) instrument…without an RNA extraction kit (p. 22727, Abstract).
Ganguli also teaches “the sample is acquired from the patient using a nasopharyngeal (NP) swab. Then, the swab is transported to VTM solution and gently agitated to transfer the viruses from the swab into the VTM. Third, the swab is discarded, and aliquots from the VTM are thermally lysed (95 °C, 1 min)”(p. 22728).
Ganguli does not teach an additional treatment buffer but does teach buffers for the LAMP reaction, including bovine serum albumin (p. 22733).
Grobler, however, provides an overview of various methods of capturing biological material from the biological samples, such as blood and tissue, have been developed and are commercially available [0013-0023]. Grobler also teaches the use of a lysis buffer containing a solubilizing agent and a detergent (or more than one of these in each category) for simultaneously inhibiting coagulation of the biological sample; lysing the biological sample to release biological material from the biological sample thus making the biological material available (see reference claim 1). Grobler also teaches the addition of the chaotropic salt - guanidine isothiocyanate (see reference claim 4), phosphate buffers tris(hydroxymethyl)aminomethane (Tris) buffers containing ethylene diamine tetra-acetic acid (EDTA) (reference claim 6) as well as reducing agents such as TCEP (reference claim 11).
Fischer additionally teaches compositions and methods for collection, transport, and storage of a biological sample containing a population of nucleic acids, which can subsequently be isolated, purified and/or characterized using one or more conventional methods or assays (p. 33). Fischer teaches reference claim 1: A one-step method of maintaining the integrity of a biological sample for nucleic acid testing in solution, comprising providing an aqueous mixture at a pH of about 6 to 7 that contains: a control nucleic acid sequence, one or more chaotropes; one or more detergents; one or more reducing agents; one or more chelators; and one or more buffers, collectively and in an amount sufficient to denature proteins, inactivate nucleases, kill pathogens, and release nucleic acid from an organism or cell contained within the biological sample when contacted with the biological sample in solution.
Fischer teaches reference claim 15: The method of claim 1, wherein the one or more chaotropes are present in an amount from about 0.5 M to about 6 M; the one or more detergents are present in an amount from about 0.1% to about 1% (wt./vol.); the one or more reducing agents are present in an amount from about 0.5 mM to about 0.3 M; the one or more chelators are present in an amount from about 0.01 mM to about 1 mM; and the one or more buffers are present in an amount from about 1 mM to about 1 M. Fischer teaches about 1 to about 10 mM or 10 mM to 30 mM of a chelator (such as, e.g., EGTA, HEDTA, DTPA, NTA, EDTA) and 1.0 mM EDTA (pH 8.0). Fischer also teaches 10 to about 500 mM of a buffering agent such as Tris-HCl. Finally, Fischer teaches exemplary chaotropes include, without limitation, guanidine thiocyanate (GuSCN), guanidine hydrochloride (GuHCl), guanidine isethionate and chaotropes (each preferably present in the composition an amount from about 0.5 M to about 6 M).
Fischer also teaches reference claim 16: the one or more chaotropes comprise guanidine thiocyanate, guanidine isocyanate, guanidine hydrochloride, or any combination thereof; the one or more detergents…the one or more reducing agents…; the one or more chelators comprise…ethylenediaminetetraacetic,…sodium citrate,…or any combination thereof
the one or more buffers comprise tris(hydroxymethyl) aminomethane,…or any combination thereof. Finally, Fischer teaches the “compositions of the invention may also further optionally include one or more additional compounds or reagents including, without limitation…albuminoids (including, without limitation, ovalbumin, and the serum albumins of bovine, equine, or human origin)(p. 38).
Optimization of parameters such as molarity, pH, volume, time and temperature is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." (Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Oommen 2018 teaches extracting nucleic acids from a biological sample and incubating the first sample tube [biological sample + treatment buffer (lysis)] at a temperature from 37 to 95 degrees Celsius for a period of time, such as 2 minutes to 3 hours [0048] which is an overlapping range of temperature and time to the ones recited in claim 1 and 4. Oommen 2018 also teaches ethylene diamine tetra acetic acid for a chelating agent and Tris(hydroxymethyl)aminomethane hydrochloride for a buffering agent as a component of a lysis buffer [0048].
For the pH and molarity of EDTA and Tris-HCl where the values are close, it would have been prima facie obvious to have selected the values. Similarly, for the narrower temperature and time parameter of at 95 degrees Celsius for 2 minutes (as recited in claim 4), it would have been prima facie obvious to further adjust and optimize for the particular biological sample chosen.
One of ordinary skill in the art would have also been motivated to combine the teachings of Ganguli (biological sample, SARS-CoV-2, isothermal amplification) with those of Grobler, Fischer and Oomen 2018 (different components of buffers) to devise an optimal treatment buffer, for example, consisting of bovine serum albumin, ethylene diamine tetra acetic acid (EDTA), Tris(hydroxymethyl)aminomethane hydrochloride (Tris-HCl) , and guanidine isothiocyanate. It would be advantageous to have a buffer that lyses, stabilizes, and preserves the integrity of nucleic acids prepared from a biological sample for subsequent RNA and/or DNA isolation, detection, quantification, amplification, and/or analysis. (See MPEP 2143, Rationale A. Combining prior art elements according to known methods to yield predictable results and Rationale G, Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention).
One of ordinary skill in the art would have had a reasonable expectation of success of to combine the teachings of Ganguli (biological sample, SARS-CoV-2, isothermal amplification) with those of Grobler, Fischer and Oomen 2018 (different components of buffers) to devise an optimal treatment buffer. Likewise, one of ordinary skill in the art would have had reasonable expectation of success of heating the collected biological sample contacted with the aforementioned treatment buffer at 95 degrees Celsius for 2 minutes. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of molecular biology and nucleic acid detection, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
(new rejection, as necessitated by amendment) Claims 9, 21 are rejected under 35 U.S.C. 103 as being unpatentable over Ganguli (previously cited) in view of Plut (previously cited), in view of Fischer (previously cited), in view of Grobler (previously cited), in view of Abate (previously cited), and in view of Oomen 2018 (previously cited).
See claims 9, 21 as submitted 06/02/2026.
Ganguli teaches there are now very recent reports of the use of saliva as an alternative to the NP swab collection process. These reports have demonstrated the ability to directly detect SARS-CoV-2 from patient saliva samples using RT-PCR (5) and RT-LAMP (40) without RNA purification steps, using a larger sample volume (>60 μL). The promising results of the present study could likely be extended for use with saliva samples for noninvasive, portable, rapid, and scalable testing for COVID-19 (p. 22733).
Ganguli does not teach wherein the collected biological sample is an oral fluid sample of a porcine chew rope, where the nucleic acid analyzed detects the porcine reproductive and respiratory syndrome ribonucleic acid virus, wherein the collected biological sample is centrifuged at 2,000 x gravity in a mini centrifuge for 10 minutes (as recited in claim 7).
Plut teaches oral fluid sampling using the undyed cotton 2 strand twisted rope provided in the IDEXX Oral Fluid Collection Kit for the detection of porcine reproductive and respiratory syndrome (PRRS) ribonucleic acid virus and centrifugation at 2000 x g for 10 minutes (p. 6).
Fischer teaches 1 to about 10 mM or 10 mM to 30 mM of a chelator such as sodium citrate and diethylene triamine pentaacetic acid [DTPA].
Grobler teaches TCEP-HCl.
Abate teaches DCTA, DTPA, EDTA, and sodium citrate.
Optimization of parameters such as molarity, pH, volume, temperature and time is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results, such as the desired 48mM guanidine isothiocyanate. The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."(Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature or even time will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Oommen 2018 teaches incubating the first sample tube [biological sample + treatment buffer (lysis)] at a temperature from 37 to 95 degrees Celsius for a period of time, such as 2 minutes to 3 hours [0048] which is an overlapping range of temperature and time to the ones recited in claims 9 and 21.
One of ordinary skill in the art would have also been motivated to combine the teachings of Ganguli (biological sample, SARS-CoV-2, isothermal amplification) with those of Fischer, Grobler, Abate, and Oomen 2018 (different components of buffers) to devise an optimal treatment buffer. It would be advantageous to have a buffer that lyses, stabilizes, and preserves the integrity of nucleic acids prepared from a biological sample for subsequent RNA and/or DNA isolation, detection, quantification, amplification, and/or analysis. (See MPEP 2143, Rationale A. Combining prior art elements according to known methods to yield predictable results and Rationale G, Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention).
One of ordinary skill in the art would have had a reasonable expectation of success of to combine the teachings of Ganguli (biological sample, SARS-CoV-2, isothermal amplification) with those of Fischer, Grobler, Abate and Oomen 2018 (different components of buffers) to devise an optimal treatment buffer. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of molecular biology and nucleic acid detection, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (Zhao)(See PTO-892 Notice of References Cited) in view of Jestin (previously cited), in view of Oomen 2018, in view of Fischer (previously cited), and in view of Abate.
See claim 22 as submitted 06/02/2026.
Zhao teaches A loop-mediated isothermal amplification (LAMP) assay was used to detect PCV2 in this study…The assay did not cross-react with PCV1, porcine reproductive and respiratory syndrome virus, porcine epidemic diarrhea virus, transmissible gastroenteritis of pigs virus or rotavirus. (The implication here is that the assay can be used to test for PRRS as recited in claim 22)(p. 1, Abstract). Zhao teaches “For detection of clinical samples, the procedure of DNA extraction was omitted. Serum samples were directly used as templates in the LAMP reaction. The sensitivity of the LAMP assay was less affected by the various components of the clinical samples than was the PCR”(p. 3)… Moreover, porcine sera could be used as templates directly in the LAMP assay without DNA extraction, because the tolerance of the LAMP assay for biological substances was superior to other detection methods. Therefore, the DNA extraction step can be omitted from the LAMP assay” (p.3).
Jestin teaches 50 microliters of porcine serum where the nucleic acid analyzed detects porcine circovirus.
Oommen 2018 teaches incubating the first sample tube [biological sample + treatment buffer (lysis)] at a temperature from 37 to 95 degrees Celsius for a period of time, such as 2 minutes to 3 hours [0048] which is an overlapping range of temperature and time.
Fischer teaches Tris-HCl and both 1 to about 10 mM or 10 mM to 30 mM of a chelator such as diethylene triamine pentaacetic acid [DTPA], EDTA, and EGTA.
Abate teaches the chelators DCTA, DTPA, EDTA, EGTA.
For the pH and molarity of the chelators (EGTA, DTPA, EDTA) and Tris-HCl where the values are identical or overlapping, it would have been prima facie obvious to have selected the values.
Additionally, optimization of parameters such as molarity, pH, volume, is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." (Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
One of ordinary skill in the art would have been motivated to combine the teachings, e.g., LAMP for swine viruses in a serum sample as taught by Zhao and to try/apply a serum sample volume (that also works for porcine circovirus nucleic acid detection) as taught by Jestin and for the advantage of developing a method of direct viral, e.g., PRRS virus, nucleic acid detection from a swine herd (See MPEP 2143, Rationale A. Combining prior art elements according to known methods to yield predictable results and Rationale G. Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention).
One of ordinary skill in the art would have been motivated to formulate a treatment buffer to use on the serum by combining the Tris-HCl, DTPA, EGTA as taught by Fischer with the DCTA as taught by Abate. It would be advantageous to have a solution that has robust chelating properties as well as anticoagulating properties with inclusion of chelators/anti-coagulants like DCTA, DTPA, EDTA, EGTA and overall stabilizes, and preserves the integrity of nucleic acids prepared from a biological sample for subsequent RNA and/or DNA isolation, detection, quantification, amplification, and/or analysis. (See MPEP 2143, Rationale A. Combining prior art elements according to known methods to yield predictable results).
One of ordinary skill in the art would have had a reasonable expectation of combine the teachings, e.g., LAMP for swine viruses in a serum sample as taught by Zhao and to try/apply a serum sample volume (that also works for porcine circovirus nucleic acid detection) as taught by Jestin for the advantage of developing a method of direct viral, e.g., PRRS virus, nucleic acid detection from a swine herd. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of swine herd health sampling and porcine reproductive and respiratory syndrome ribonucleic acid virus detection, and commonly used as evidenced by the applied prior art.
One of ordinary skill in the art would have had a reasonable expectation of success of formulating a treatment buffer with DCTA, DTPA, EDTA, EGTA and Tris-HCl. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of molecular biology and nucleic acid detection, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claims 14, 23 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao in view of Lopez (previously cited), in view of Shaw (previously cited), and in view of Oomen 2018.
See claims 14, 23 as submitted 06/02/2026.
Zhao teaches A loop-mediated isothermal amplification (LAMP) assay was used to detect PCV2 in this study… The assay did not cross-react with PCV1, porcine reproductive and respiratory syndrome virus, porcine epidemic diarrhea virus, transmissible gastroenteritis of pigs virus or rotavirus. (The implication here is that the assay can be used to test for PRRS as recited in claim 22)(p. 1, Abstract). Zhao teaches “For detection of clinical samples, the procedure of DNA extraction was omitted. Serum samples were directly used as templates in the LAMP reaction”(p. 3).
Zhao does not teach porcine processing fluid.
Lopez teaches collecting from swine and detection from porcine processing fluid. Lopez teaches “processing fluid samples are easily collected under field conditions and provide the means to test more piglets more frequently in a practical way, thereby improving PRRSV surveillance…[and] [t]he objective of this field-based study was to determine the relationship between viremic piglets and the detection of PRRSV RNA in processing fluid sample. Lopez further teaches, “[p]rocessing fluid represents a practical, reliable and efficient method to surveil breeding herds for PRRSV because it allows for continuous surveillance at a low cost”(Abstract). Lopez compared both serum and processing fluid samples (p. 2). Lopez also mixed the sample and a lysis solution (200 µl, 1:1 ratio). This was done before combining with a bead solution and continuing on with an extraction process, and RT-qPCR.
Shaw explains the standard sample buffer constituents and illustrates a series of protocols for processing diverse samples for two-dimensional gel electrophoresis, including
hydrophobic membrane proteins. Current methods for concentrating lower abundance
proteins, by removal of high abundance proteins, are also outlined (p. 1408). Shaw also teaches a solution with [magnesium chloride] MgCl2 (5 mM ), [potassium chloride] KCl (25 mM), and 50 mM Tris-HCl pH 7.4. (p. 1413). Shaw also teaches a solubilization buffer for the preparation of Chinese hamster ovary cells with the added reducing reagent (reduction of disulphide bonds aids solubilization of complex mixtures of proteins) component of 2mM TCEP-HCl (p. 1411).
Oommen 2018 teaches incubating the first sample tube [biological sample + treatment buffer (lysis)] at a temperature from 37 to 95 degrees Celsius for a period of time, such as 2 minutes to 3 hours [0048] which is an overlapping range of temperature and time.
For the time and temperature where the values are identical or overlapping, it would have been prima facie obvious to have selected the values.
Optimization of parameters such as molarity, pH, volume, is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." (Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
One of ordinary skill in the art would have been motivated to (1) try processing fluid as taught by Lopez instead of serum as taught by Zhao for the loop-mediated isothermal amplification (LAMP) assay; (2) formulating a treatment buffer with MgCl2, KCl, Tris-HCl, and TCEP-HCl as taught by Shaw; and (3) heating the collected biological sample with the treatment buffer as taught by Oomen 2018 for the advantage of developing a method of direct viral, detection in a swine herd (See MPEP 2143 Rationale G. Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention).
One of ordinary skill in the art would have had a reasonable expectation of success to (1) try processing fluid as taught by Lopez instead of serum as taught by Zhao for the loop-mediated isothermal amplification (LAMP) assay as well as (2) formulating a treatment buffer with MgCl2, KCl, Tris-HCl, and TCEP-HCl as taught by Shaw; and (3) heating the collected biological sample with the treatment buffer as taught by Oomen 2018. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of molecular biology and nucleic acid detection, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Liu et al. (Liu)(See PTO-892 Notice of References Cited), in view of Lui (previously cited), in view of Collier, in view of Fischer (previously cited), and in view of Oommen 2018 (previously cited).
See claim 24 as submitted 06/02/2026.
Liu teaches “a Direct-LAMP procedure, amplifying nucleic acids with various samples (including whole blood, dried blood spot, buccal swab and saliva) without DNA purification, which is essential for conventional nucleic acid detection methods. The turnaround time was about 30 min from sample collection to provision of results. MTHFR C677T, and ALDH2 Glu504Lys were utilized as models for SNP detection with the Direct-LAMP method. Accuracy was evaluated against clinical samples, and complete consistency between genotyping results reveals that this Direct LAMP procedure generally concords with sequencing (p. 71).
Liu does not teach universal transport medium. Liu also only teaches NaOH as a treatment buffer.
Lui teaches methods, devices, systems, fluidic devices, and kits for detection of genetic diseases caused by or related to a subject's genetic characteristics [Abstract, 0001]. Lui also teaches a transport medium such as the Copan Universal transport Medium (UTM-RT) for biological sampling [0088].
Collier teaches a cheek swab, that the second most prevalent mutation in the same hemochromatosis gene is a C to G transversion in exon 2, known as H63D and also teaches a method of nucleic acid detection of the genetic mutation.
Fischer teaches compositions and methods for collection, transport, and storage of a biological sample containing a population of nucleic acids, which can subsequently be isolated, purified and/or characterized using one or more conventional methods or assays (p. 33). Fischer teaches reference claim 1: A one-step method of maintaining the integrity of a biological sample for nucleic acid testing in solution, comprising providing an aqueous mixture at a pH of about 6 to 7 that contains: a control nucleic acid sequence, one or more chaotropes; one or more detergents; one or more reducing agents; one or more chelators; and one or more buffers, collectively and in an amount sufficient to denature proteins, inactivate nucleases, kill pathogens, and release nucleic acid from an organism or cell contained within the biological sample when contacted with the biological sample in solution. Fischer also teaches EDTA, guanidine isothiocyanate, and Tris-HCl.
Oomen 2018 teaches incubating the first sample tube at a temperature from 37 to 95 degrees Celsius for a period of time, such as 2 minutes to 3 hours [0048].
For the time and temperature where the values are identical or overlapping, it would have been prima facie obvious to have selected the values.
Optimization of parameters such as molarity, pH, volume, is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient needed to achieve the desired results. The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages." (Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
One of ordinary skill in the art would have been motivated to try the universal transport medium during sample collection as taught by Lui with an oral swab to exploit its broader cellular stabilization properties for improved detection not only for microbes but also human genetic mutations. Similarly, one of ordinary skill would have been motivated to formulate and optimize a treatment buffer with reagents as taught by Fischer and by heating as taught by Oomen 2018 for the advantage of processing (lysis), facilitating solubilization, stabilizing, and preserving the integrity of nucleic acids prepared from a biological sample for subsequent loop isothermal amplification as taught by Liu (See MPEP 2143, Rationale A. Combining prior art elements according to known methods to yield predictable results and Rationale G. Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention).
One of ordinary skill in the art would have had a reasonable expectation of success of using the universal transport media for specimen collection, combining known chelating agents and reducing agents to formulate a treatment buffer that would facilitate solubilization, stabilize, and preserve the integrity of nucleic acids prepared from a biological sample for subsequent RNA and/or DNA isolation, detection, quantification, amplification, and/or analysis. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of clinical patient sampling, sample transport, molecular biology sample preparation techniques, to include genetic testing, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Wee et al. (Wee)(See PTO 892 Notice of References Cited) teaches rapid direct nucleic amplification test without RNA extraction for SARS-CoV-2 (title). Wee teaches “PCR directly from crude samples without nucleic acid purification has been attempted before using inhibitor-resistant enzymes, modified buffers and additives in the mastermix. Our group…and others…have previously detected whole dengue virus in a single tube reaction containing serum and plasma in up to 8% (v/v). Direct amplification from samples has also been reported for the detection of other RNA viruses, including African Chikungunya virus…noroviruses…and bovine viral diarrhea virus…and from a variety of matrices, including serum, throat swab and feces…However, the presence of PCR inhibitors, such as mucin and proteins, poses a challenge for direct amplification from respiratory samples…and there are limited studies amplifying coronaviruses directly from such specimens. We have developed a DIRECT-PCR protocol using widely used and validated PCR primers, established its analytical performance with both DNA and RNA templates in respiratory samples, and transferred the protocols from benchtop to a portable thermocycler (p.2).
No claims 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Claire Cornelius whose telephone number is (571)272-0860. The examiner can normally be reached M-F, 0930-1700.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas J. Visone can be reached at (571) 270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/C.C./Examiner, Art Unit 1671
/M FRANCO G SALVOZA/Primary Examiner, Art Unit 1672
Prosecution Insights