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
1. Claims 1-20 are under consideration.
Priority
2. This application claims benefit of priority to United States Provisional Patent Application No. 63/088,347 filed October 6, 2020, entitled “Method for Detection of RNA or DNA from Biological Samples”.
Information Disclosure Statement
3. The information disclosure statement (IDS) was submitted on 04/05/2023. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Interpretation
4. Claim 1 recites “from a biological sample without isolation or purification of the nucleic acids”. Isolation or purification is interpreted literally as “without isolation or purification of nucleic acids from other cellular components through centrifuge or magnetic beads, or without two or more centrifuge steps, with one centrifuge step separating cells containing nucleic acids for analysis from a supernatant and a second centrifuge step separating cellular debris from nucleic acids) prior to analysis” as detailed in the specification [0012].
Specification
5. 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.
Claim Objections
6. 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.
Claim Rejections - 35 USC § 112
7. 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.
8. Claims 1-20 are rejected under 35 U.S.C. 112 (b) 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.
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. (See PTO-892: Notice of References 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).
9. 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.
10. 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. Claim 16 recites the method of claim 12, wherein the treatment buffer is a volume equal to the volume of the universal transport media comprising 0.5 mM ethylene diamine tetra acetic acid of pH 8, 80 mM Guanidine isothiocyanate, and 10mM Tris(hydroxymethyl)aminomethane hydrochloride of pH 9.0, and wherein the heating comprises heating the collect biological sample contacted with the treatment buffer at 95 degrees Celsius for 2 minutes. Claim 12 does not mention universal transport media, however, claim 15 does. It appears that claim 16 should be dependent on claim 15 and not claim 12. As If so, then claim 16 should recite instead “The method of claim 15, wherein…”.
Claim Rejections - 35 USC § 101
11. 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.
12. Claims 1-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
See claims 1-20 as submitted 04/05/2023.
In view of the 2019 PEG (“The 2019 Revised Patent Subject Matter Eligibility Guidance” (2019 PEG) found at https://www.govinfo.gov/content/pkg/FR-2019-01-07/pdf/2018-28282.pdf ), based upon an analysis with respect to the claims as a whole, claim 1 does not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
The claims do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more these claims are interpreted in light of the most recent Guidelines (See “Subject Matter Eligibility” found at https://www.uspto.gov/patent/laws-and-regulations/examination-policy/subject-matter-eligibility ; as well as Subject Matter Eligibility Examples: Life Sciences at https://www.uspto.gov/sites/default/files/documents/ieg-may-2016-ex.pdf )
These claims are analyzed for eligibility in accordance with their broadest reasonable interpretation. In view of the Subject Matter Eligibility Test for Products and Processes and the Steps cited below (See flowchart at pages 10-11 at https://www.uspto.gov/sites/default/files/documents/peg_oct_2019_update.pdf ), the claims are directed to an abstract idea as further detailed below.
In view of the Subject Matter Eligibility Test for Products and Processes and the Steps cited below, the claims are directed to a process or processes (Step 1); an abstract idea, which sets forth a judicial exception.
In this case, the claims recite or are directed to a process (Step 1) and recites “analyzing the biological sample for the nucleic acid” that is directed to judicial exceptions (in this case, an abstract idea)(Step 2A). The step of “analyzing” could be performed by a human using mental steps or basic critical thinking, which are types of activities that have been found by the courts to represent abstract ideas (e.g., the mental comparison in Ambry Genetics, or the diagnosing an abnormal condition by performing clinical tests and thinking about the results in Grams). Thus, the claim is directed to at least one exception (Step 2A: YES), which may be termed an abstract idea. (See MPEP 2106.04(a) III B - B. A Claim That Encompasses a Human Performing the Step(s) Mentally With or Without a Physical Aid Recites a Mental Process).
Thus the claims are directed to a judicial exception, and the claims as a whole are focused on an abstract idea (See also Example 29, Claim 2 (Diagnosing and Treating Julitis) of the Subject Matter Eligibility Examples: Life Sciences found at https://www.uspto.gov/sites/default/files/documents/ieg-may-2016-ex.pdf).
The claim as a whole is focused on “analyzing the biological sample for nucleic acid” and not on the products (e.g., the biological sample) per se. Thus, there is no need to perform the markedly different characteristics analysis.
Further as to Step 2A in view of the 2019 PEG, in view of Prong 1 of Revised Step 2A, the claims recite an abstract idea.
As to Prong 2 of Step 2A, the instant claims do not recite additional elements that integrate the judicial exception (abstract idea) into a practical application. “Integration into a practical application” requires an additional element(s) or combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes meaningful limit on the judicial exception, such that the claim is more than a drafting effort designed to monopolize the exception (See for example, Slide 18 of 2019 PEG training at http://ptoweb.uspto.gov/patents/exTrain/101.html ).
Further, in view of Step 2B and the “No” pathway, the claims do not recite additional elements that amount to significantly more than the judicial exception. The instant claims recite: contacting, and heating which are well-understood, routine and conventional activities in view of the dependent references cited below (See Oommen 2018 in view of Fischer as cited below). Further, the steps are recited at a high level of generality. The instant claims merely instruct one to “analyzing the biological sample for the nucleic acid”. When recited at this high level of generality, there is no meaningful limitation that distinguishes it from well-understood, routine and conventional activity engaged in by scientists prior to applicant’s invention.
Consideration of the additional elements as a combination also adds no other meaningful limitations to the exception not already present when the elements are considered separately. The claims do not invoke any of the considerations that courts have identified as providing significantly more than the exceptions. Even when viewed as a combination, the additional elements fail to transform the exceptions into a patent eligible application of that exception. Thus, the claims as a whole do not amount to significantly more than the exception.
Thus, it is asserted that the claims are directed to judicial exceptions (by reciting mental steps associated with production steps as part of routine and conventional steps known in the art) without reciting more or additional elements that amount to significantly more than the judicial exception.
Therefore claims 1 and 17 do not recite eligible subject matter under 35 U.S.C. 101 in view of the Subject Matter Eligibility Test for Products and Processes, and the claimed invention is directed to non-statutory subject matter.
Claim Rejections - 35 USC § 103
13. 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.
14. 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.
15. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
16. Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable by Oommen (“Oommen 2018”)(US2018/0105809 A1) (See PTO-892: Notice of References Cited).
Claim 1 as submitted 04/05/2023.
Regarding “human, animal, microbial, and viral”, nucleic acid is nucleic acid, no matter the source.
Oommen 2018 teaches Fig. 2 illustrates a method 200 for extracting nucleic acids from a biological sample. The biological sample may be blood, muscle tissue, plasma, semen cells, cheek swabs, nasal swabs, hair follicles, buffer wash from a biological specimen, and preserved biological samples including frozen samples. In 201, the biological sample having nucleic acids is treated to extract nucleic acids with a lysis buffer. When the biological sample includes durable tissue, such as muscle tissue, ear notches, tail clippings, or hair follicles, the treating may still further include 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]. In Fig. 2/ 206, the eluted nucleic acid is analyzed . Analysis may include quantitative and qualitative analysis, such as absorption analysis, polymerase chain reaction (PCR) amplification, optionally followed by gel electrophoresis [0054].
For the time and temperature where the values are overlapping to those taught by Oommen 2018, it would have been prima facie obvious to have selected the values.
Additionally, 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).
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.
17. 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).
Claims 2 and 5 as submitted 04/05/2023.
Oommen 2018 teaches the method of claim 1. Oommen 2018 also teaches cheek swabs [0048] which is a type of oral swab.
Oommen 2018 does not teach a nasal swab from a human collected into a volume of viral transport media solution, where the nucleic acid analyzed detects the SARS-Cov2 ribonucleic acid virus. Oommen 2018 also does not teach the collected biological sample is an oral swab from a human collected into 500 microliters of the treatment buffer, where the nucleic acid analyzed detects the SARS-Cov2 ribonucleic acid virus.
Ganguli teaches: For diagnostic testing of SARS-CoV-2 from humans, the current clinical workflow includes collecting NP/nasal specimens from human patients using swabs which are immediately transferred into a sterile transport tube, containing 2 ml to 3 ml of VTM [viral transport media], for storage until diagnostic assays can be performed” (p. 22729). Ganguli also teaches the nucleic acid analyzed detects the SARS-CoV-2 ribonucleic acid virus via rapid reverse transcription loop mediated isothermal amplification (RT-LAMP) and a portable detection system (Abstract) (as recited in claim 2).
Ganguli also teaches: In Fig 2. Detection of SARS-CoV-2 virus from mock NP swabs transported to VTM (A), a swab is inserted into a tube with virus-spiked nasal fluid and absorbs the fluid. After vigorously mixing the swab in 100µl or 500µl of VTM (as recited in claim 5), an aliquot of the VTM sample is thermally lysed at 95°C for 1 min. Ganguli does not teach an oral swab from a human. However, Ganguli does teach that the “promising results of the present study could likely be extended for use with human saliva samples for noninvasive, portable, rapid, and scalable testing for COVID-19.
One of ordinary skill in the art would have been motivated to develop a method of direct viral, e.g., SARS-CoV-2 nucleic acid detection from a human patient clinical sample (nasal swab) as taught by Ganguli for the benefit of making a quicker clinical diagnosis (See MPEP 2143, A. and 2143.02: Combining prior art elements according to known methods to yield predictable results).
One of ordinary skill in the art would have also been motivated to combine Oommen 2018’s teachings from (claim 1) and the Ganguli teachings to arrive at the strategy to use a human oral swab as the biological sample, collect into a 500 microliters of the treatment buffer, where the nucleic acid analyzed detects the Sars-Cov2 ribonucleic acid virus as taught by Ganguli because this strategy would decrease the likelihood of patient discomfort and injury (particularly in comparison to the nasopharyngeal collection route), would be an easier and less invasive technique, and because plausibly, patients may even be able to do to do the swabbing themselves (e.g., so less labor intensive for medical professionals and potentially less person-to-person contact in the event of an infectious disease target).
One of ordinary skill in the art would have had a reasonable expectation of success of employing nasal swabs and VTM for the collected biological sample and then more specifically analyzing the biological sample for the nucleic acid of SARS-CoV-2. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in the context of human diagnostic sample collection and diagnostic testing, 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 for using a human oral swab as the biological sample, collect into a 500 microliters of the treatment buffer, where the nucleic acid analyzed detects the Sars-Cov2 ribonucleic acid virus as taught by Ganguli. There would have been reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the 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.
18. 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)(See PTO-892: Notice of References Cited).
Claims 3 and 4 as submitted 04/05/2023.
Oommen 2018 and Ganguli teach the method of claims 1 and 2. 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 claim 4. Oommen 2018 also teaches ethylene diamine tetra acetic acid for a chelating agent and Tris(hydroxymethyl)aminomethane hydrochloride for a buffering agent as possible components of a lysis buffer [0048].
Oommen 2018 does not teach percentage, molarity, pH specifics wherein the treatment buffer comprises 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.
Fischer teaches the serum albumins of bovine, equine, or human origin. 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) (as listed in claim 3), guanidine hydrochloride (GuHCl), guanidine isethionate and chaotropes (each preferably present in the composition an amount from about 0.5 M to about 6 M). According to Millipore Sigma (See PTO-892: Notice of References Cited), synonyms for isothiocyanate include GITC, GTC, Guanidine thiocyanate, Guanidinium isothiocyanate, Guanidinium rhodanide, and Guanidinium thiocyanate.
One of ordinary skill in the art would have also been motivated to formulate a treatment buffer consisting of bovine serum albumin, ethylene diamine tetra acetic acid (EDTA), Tris(hydroxymethyl)aminomethane hydrochloride (Tris-HCl) , and guanidine isothiocyanate (as recited in claim 3) as taught by Oommen 2018 and Fischer. 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, A. and 2143.02: 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 success of formulating a treatment buffer consisting of bovine serum albumin, ethylene diamine tetra acetic acid (EDTA), Tris(hydroxymethyl)aminomethane hydrochloride (Tris-HCl) , and guanidine isothiocyanate as taught by Oomen 2018 and Fischer. 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.
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.
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).
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.
19. 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).
Claim 6 as submitted 04/05/2023.
Oommen 2018 and Ganguli teach claims 1 and 5. 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 claim 6.
Oommen 2018 and Ganguli do not teach molarity and pH specifics wherein the treatment buffer comprises 0.25 mM Sodium Citrate pH 6.7 and 2 mM Tris(2- carboxyethyl)phosphine hydrochloride (TCEP-HCl).
Fischer teaches 1 to about 10 mM or 10 mM to 30 mM of a chelator such as sodium citrate.
Grobler teaches various methods of capturing biological material from the biological samples, such as blood and tissue, have been developed and are commercially available. For example, U.S. Pat. No. 5,346,994 discloses a method of isolating substantially pure RNA, DNA and proteins from biological tissue, comprising the steps of: (f) precipitating DNA from the interphase by the addition of CsCl, sodium citrate solution and a lower alcohol thereto and recovering the precipitated DNA by sedimentation [0013]. Grobler also teaches the method may include the step of concomitantly adding a reducing agent selected from the group consisting of 2-mecarptoethanol, dithiothreitol (DTT), 2-mercaptoethylamine, tris(2-carboxyl)phosphine (TCEP), cysteine HCl, N-ethylmaleimide, Nacystelyn, dornase alfa, thymosin β4, guaifenesin TCEP-HCl, and combinations thereof, to the biological sample together with the lysis buffer containing the solubilizing agent and the detergent [0042]. Guaifenesin is a drug (mucolytic just as Nacystelyn is listed above), not a reducing agent, and so in this example, it would have been a presumed additive to the base TCEP-HCl solution or in fact, there may be a punctuation (missing comma) issue in the prior art. Guaifenesin and some of the other substances listed above may have been explored for their ability to increase volume and reduce viscosity of oral samples potentially laced with sputum.
One of ordinary skill in the art would have also been motivated to formulate a treatment buffer with both sodium citrate as taught by Fischer and Grobler and TCEP-HCl as taught by Grobler. It would be advantageous to have a buffer that facilitates 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, A. and 2143.02: 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 success of formulating a treatment buffer consisting of sodium citrate and TCEP-HCl as taught by Fischer and Grobler. 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.
For the narrower temperature and time parameter of at 95 degrees Celsius for 2 minutes (as recited in claim 6), it would have been prima facie obvious to further adjust and optimize for the particular biological sample chosen.
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. 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 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.
20. 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”) (See PTO-892: Notice of References Cited)
Claim 7 as submitted 04/05/2023.
Oommen 2018 teaches the method of Claim 1.
Oommen 2018 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)(as recited in claim 7).
One of ordinary skill in the art would have been motivated to combine the teachings, particularly the saliva collection via twisted rope as taught by Plut for the advantage of developing a method of direct viral, e.g., PRRS virus nucleic acid detection from a swine herd. The twisted rope method to collect saliva would be particularly advantageous to reduce sampling stress for the swine (who are prone to malignant hyperthermia or porcine stress syndrome (PSS)), swine handlers, and sampler, and advantageous for making a quicker diagnosis of a herd health problem (See MPEP 2143, A. and 2143.02: 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 success of using the oral fluid from an undyed cotton 2 strand twisted rope as the collected biological sample, to centrifuge it, and where the nucleic acid analyzed detects the porcine reproductive and respiratory syndrome ribonucleic acid virus as taught by Plut. 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.
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.
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) (See PTO-892: Notice of References Cited).
Claims 8 and 9 as submitted 04/05/2023.
Oommen 2018 and Plut teach claims 1 and 7. 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 claim 9.
Oommen 2018 and Plut do not teach wherein the treatment buffer comprises a volume equal to a volume of the collected biological sample or specific pH and molarity of 2 mM 1,2-Cyclohexanedinitrilotetraacetic acid [DCTA] of pH 8, from 4 mM diethylenetriaminepentaacetic acid [DTPA] of pH 8, 1 mM ethylene diamine tetra acetic acid [EDTA] of pH 8, 5 mM Sodium Citrate of pH 6.5, 2 mM Tris(2-carboxyethyl)phosphine hydrochloride [TCEP-HCl].
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.
One of ordinary skill in the art would have been motivated to formulate a treatment buffer by combining the molarity as taught by Fischer, TCEP-HCl as taught by Grobler with the DCTA, DTPA, EDTA and sodium citrate as taught by Abate. It would be advantageous to have a solution that lyses, has robust chelating properties with inclusion of chelators like DCTA, DTPA, EDTA, and sodium citrate, 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, A. and 2143.02: 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 success of formulating a treatment buffer with chelators such as DCTA, DTPA, EDTA, sodium citrate with TCEP-HCl. 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, rich with chelating agents, at 80 degrees Celsius for 10 minutes. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated in molecular biology and nucleic acid detection, and commonly used as evidenced by the applied prior art.
For the narrower temperature and time parameter of at 80 degrees Celsius for 10 minutes (as recited in claim 9), it would have been prima facie obvious to further adjust and optimize for the particular biological sample chosen.
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 (to achieve the vol, pH and molarity as recited in claim 8). 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).
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.
22. 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).
Claim 10 as submitted 04/05/2023.
Oommen 2018 teaches claim 1.
Oommen 2018 does not teach wherein the collected biological sample is 50 microliters of porcine serum where the nucleic acid analyzed detects the porcine reproductive and respiratory syndrome ribonucleic acid virus (as recited in claim 10).
Plut teaches porcine serum samples used for the detection of porcine reproductive and respiratory syndrome (PRRS) (as recited in claim 10) and Porcine Circovirus 2 (PCV2).
Jestin teaches 50 microliters of porcine serum where the nucleic acid analyzed detects porcine circovirus.
One of ordinary skill in the art would have been motivated to combine the teachings, e.g., the porcine serum sample as taught by Plut and Jestin 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. (See MPEP 2143, A. and 2143.02: 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 success of using a the porcine serum sample as taught by Plut and Jestin and to try/apply a serum sample volume as taught by Jestin. 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.
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.
23. 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 (See PTO-892: Notice of References Cited).
Claim 11 as submitted 04/05/2023.
Oommen 2018, Plut, and Jestin teach claims 1 and 10. 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 claim 11.
Oommen 2018, Plut, and Jestin do not teach wherein the treatment buffer is 50 microliters of 2 mM 1,2-Cyclohexanedinitrilotetraacetic acid [DCTA] of pH 8, 4 mM diethylenetriaminepentaacetic acid [DTPA] of pH 8, 1 mM ethylene diamine tetra acetic acid [EDTA] of pH 8, 1 mM ethylene glycol-bis(O-aminoethyl ether)-N,N,N',N'-tetraacetic acid [EGTA] of pH 8, 10 mM Tris(hydroxymethyl)aminomethane hydrochloride [Tris-HCl] of pH 9.0, and wherein the heating comprises heating the collected biological sample contacted with the treatment buffer at 95 degrees Celsius for 2 minutes.
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.
One of ordinary skill in the art would have been motivated to formulate a treatment buffer 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, A. and 2143.02: 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 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.
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).
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.
24. 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).
Claim 12 as submitted 04/05/2023.
Oommen 2018 teaches Claim 1.
Oommen 2018 does not teach wherein the collected biological sample is 50 microliters of porcine processing fluid where the nucleic acid analyzed detects the porcine reproductive and respiratory syndrome ribonucleic acid virus.
Fischer teaches porcine (as a patient) and serum (as the biological sample). Fischer also teaches 50 microliters of serum in his section, Preparation of Serum Samples for Assay.
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).
One of ordinary skill in the art would have been motivated to collect and detect porcine reproductive and respiratory syndrome virus from porcine processing fluid as taught by Lopez, and to use a sample volume amount similar to that of porcine serum, e.g., 50 microliters as taught by Fischer, in order to reduce sampling stress and to make a quicker diagnosis for a herd health problem (See MPEP 2143, A. and 2143.02: Combining prior art elements according to known methods to yield predictable results; See MPEP 2143, 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 trying 50 microliters of sample, as taught by Fischer, where the sample collected is instead porcine processing fluid. And one of ordinary skill in the art would have had a reasonable expectation of success of detecting the porcine reproductive and respiratory syndrome ribonucleic acid virus from the nucleic acid analyzed as taught by Lopez. 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.
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.
25. 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”)(See PTO-892: Notice of References Cited).
Claims 13 and 14 as submitted 04/05/2023.
Oommen 2018, Fischer, and Lopez teach claims 1 and 12. Oommen 2018 teaches the treating may still further include 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 14).
Oommen 2018, Fischer, and Lopez do not teach wherein the treatment buffer comprises 50 microliters of 3 mM magnesium chloride, 75 mM potassium chloride, 50 mM Tris(hydroxymethyl)aminomethane hydrochloride of pH 9.0, and from 5.0 mM mM Tris(2-carboxyethyl)phosphine hydrochloride, where the treatment buffer is adjusted to pH 8.3.
Shaw 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).
One of ordinary skill in the art would have been motivated to formulate a treatment buffer by combining the agents MgCl2, KCl, Tris-HCl, and TCEP-HCl as taught by Shaw. It would be advantageous to have a buffer that can improve 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. (See MPEP 2143, A. and 2143.02: 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 success of formulating a treatment buffer with MgCl2, KCl, Tris-HCl, and TCEP-HCl as taught by Shaw. 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.
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