Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 109-112, 114-129 and 131-141 are currently pending. Claims 109-111, 116 and 128 have been amended by Applicants’ amendment filed 12-16-2025. Claim 113 and 130 have canceled by Applicants’ amendment filed 12-16-2025. Claim 141 has been added by Applicants’ amendment filed 12-16-2025.
Applicant's election of Group I with traverse of claims 109-113, 116, 125 and 130, directed to a quality control composition used to assess the functionality of a Nucleic Acid Test (NAT); and the election with traverse of Species as follows:
Species (A): wherein the second target nucleic acid sequence is characteristic of some members of the species or genus of the organism to be tested (claim 111), in the reply filed October 23, 2023 was previously acknowledged.
Claims 114-115, 117-122, 124, 126-129 and 131-139 were previously withdrawn by Applicant from further consideration pursuant to 37 CFR 1.142(b) in the reply filed October 23, 2023 as being drawn to a non-elected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on October 23, 2023.
Claims 112 and 125 were previously withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected species, there being no allowable generic or linking claim.
The restriction requirement was deemed proper and was made FINAL.
The claims will be examined insofar as they read on the elected species.
A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144) See MPEP § 821.01.
Therefore, claims 109-111, 116, 123, 140 and 141 are under consideration to which the following grounds of rejection are applicable.
Priority
The present application filed November 18, 2020 is a 35 U.S.C. 371 national stage filing of International Application No. PCT/CA2019/050689, filed May 21, 2019, which claims the benefit of US Provisional Patent Application 62/673,480, filed May 18, 2018.
Withdrawn Objections/Rejections
Applicants’ amendment and arguments filed December 16, 2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or
objection not specifically addressed below are herein withdrawn.
Maintained Objections/Rejections
Claim Rejections - 35 USC § 112(b)
The rejection of claims 109-111, 116, 123 and 140 is maintained, and claim 141 is newly rejected, under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claims 109-111, 116 and 141 are indefinite because the claims appear to recite both a product and process in the same claim. The examiner cautions that according to the MPEP 2173.05(p)(II) states that a single claim which claims both an apparatus and the method steps of using the apparatus is indefinite under 35 U.S.C. 112(b). PXL Holdings v. Amazon.com, Inc., 430 F.2d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005); Ex parte Lyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990) (claim directed to an automatic transmission workstand and the method of using it held ambiguous and properly rejected under 35 U.S.C. 112(b)). For example, claim 109 recites: “a quality control composition” in line 1; “at least one first protected nucleic acid sequence in a protecting vehicle comprising a first nucleic acid sequence” in lines 5-6; “at least one second protected nucleic sequence in a separate protecting vehicle comprising a second nucleic acid sequence” in lines 9-10; and “wherein each of the separate protecting vehicles are: (i) any enclosing substance or enclosing barrier, wherein the separate protecting vehicles are independently selected from the group consisting of a virus, a virus-like particle, a bacterium, a eukaryotic cell, or an inactivated, non-viable or non-pathogenic organism” in lines 17-23; while claim 109 also recites: “which is characteristic of a second target nucleic acid sequence in the test article being tested in the NAT” in lines 10-11; “so that the at least one first protected nucleic acid sequence and the at least one second protected nucleic acid sequences are recovered in a nucleic acid extraction step of the NAT” in lines 26-28; and “wherein the NAT detects at least one of a presence of and/or characteristics of an organism to be tested for in a test article by detecting the first and second target nucleic acid sequences in the test article” in lines 34-36. Such claims can also be rejected under 35 U.S.C. 101 based on the theory that the claim is directed to neither a “process” nor a “machine,” but rather embraces or overlaps two different statutory classes of invention set forth in 35 U.S.C. 101 which is drafted so as to set forth the statutory classes of invention in the alternative only. Id. at 1551.
Claim 109 is indefinite for the recitation of the term “the first protected nucleic acid sequence and/or second protected nucleic acid sequence” in claim 109, lines 18-19. There is insufficient antecedent basis for the term “the first protected nucleic acid sequence and/or second protected nucleic acid sequence” in the claim because claim 109, lines 5 and 9 recite the terms “at least one first protected nucleic acid sequence” and “at least one second protected nucleic acid sequence.”
Claim 109 is indefinite for the recitation of the term “the protecting vehicles” such as recited in claim 109, line 20. There is insufficient antecedent basis for the term “the protecting vehicles” in the claim because claim 109, lines 8, 16 and 24 recite the terms “a protecting vehicle;” “separate protecting vehicles” and “same or different types of protecting vehicle.”
Claim 109 is indefinite for the recitation of the term “the target nucleic acid sequences” such as recited in claim 109, line 33. There is insufficient antecedent basis for the term “the target nucleic acid sequences” in the claim because claim 109, line 3 recites the term “a target nucleic acid sequence.”
Claim 109 is indefinite for the recitation of the term “the first and second target nucleic acid sequences” such as recited in claim 109, lines 35-36. There is insufficient antecedent basis for the term “the first and second target nucleic acid sequences” in the claim because claim 109, lines 3, 5-6 and 12-13 recites the terms “a target nucleic acid sequence;” “a first nucleic acid sequence;” “a second nucleic acid sequence.”
Claim 109 is indefinite for the recitation of the term “characteristics of an organism to be tested for in a test article” such as recited in claim 109, lines 35-36. There is insufficient antecedent basis for the term “an organism” in the claim because claim 109, lines 3-4 recites the term “a viable or pathogenic organism.” Moreover, claim 109 does not recite the presence of an organism in the test article, such that the origin, purpose and/or physical presence of the “organism” in the quality control composition is unclear and, thus, the metes and bounds of the claim cannot be determined.
Claim 111 is indefinite for the recitation of the term “an organism” such as recited in claim 111, lines 3, 8 and 11. There is insufficient antecedent basis for the term “an organism” in the claim because the protecting vehicles recited in claim 109, lines 21-23 include “a virus…an inactivated, non-viable or non-pathogenic organism.” Moreover, a preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone. See In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976) and Kropa v. Robie, 187 F.2d 150, 152, 88 USPQ 478, 481 (CCPA 1951). As noted supra, instant claim 109 does not recite the presence of an organism in a test article and, thus, the metes and bounds of the claim cannot be determined.
The rejection of claim 111 is maintained as being indefinite for the recitation of the term “nucleic acid sequence protection properties” such as recited in claim 111, line 4 because claim 111 depends from claim 109, where claim 109 does not recite any protecting properties. Thus, it is unclear how an organism comprises nucleic acid sequence protection properties; what the protecting properties are when processed through a NAT; and/or how these properties are the same as, or are similar to those in an unidentified organism tested for in an unidentified test article and, thus, the metes and bounds of the claim cannot be determined.
The rejection of claim 111 is maintained as being indefinite for the recitation of the term “similar to” in claim 111, line 5 because the term “similar to” is relative term that renders the claim indefinite. The term “similar to” is not defined by the claim, and the Specification does not provide a standard for ascertaining the requisite amount of ‘similarity’ an organism has with regard to unrecited “protection properties” when processed through the NAT as compared to some other unidentified organism, such that one of ordinary skill in the art would not be reasonably appraised of the scope of the invention.
The rejection of claim 116 is maintained as being indefinite for the recitation of the terms “the first protected nucleic acids;” and “the second protected nucleic acid” such as recited in claim 116, lines 8-12. There is insufficient antecedent basis for the terms “the first protected nucleic acids” and “the second protected nucleic acid” in the claim because claim 1, lines 5 and 9 recite the terms “at least one first protected nucleic acid sequence” and “at least one second protected nucleic acid sequence,” claim 116, line 7 recites the term “two first protected nucleic acid sequences.”
Claim 123 is indefinite for the recitation of the terms “detecting an organism” and “a test sample suspected of comprising the organism” such as recited in claim 123, lines 1, 3 and 11 because it is unclear whether the quality control composition of claim 109 can be used in the method of claim 123 given that claim 109 recites the presence of nucleic acids and test articles, but does not recite the presence of “organisms” and/or “test samples”. It is unclear how the functionality of a NAT can be assessed with respect to an organism in a sample as recited in claim 123, when using the quality control composition of claim 109 and, thus, the metes and bounds of the claim cannot be determined.
Claim 123 is indefinite for the recitation of the term “comparing results…detecting the quality control composition in the NAT and detecting the target nucleic acid sequence or organism in the NAT of the test sample assesses functionality of the NAT” in claim 123, lines 8-11 because it is unclear how functionality is determined when the comparison of the results is not equivalent. The NAT of the quality control composition comprises detecting nucleic acids within the same or different types of protecting vehicles, while the NAT of the test sample detects target nucleic acid sequences or organisms, such that it is completely unclear how comparing the results of a NAT of the quality control composition to a NAT of a test sample will provide an assessment of NAT functionality and, thus, the metes and bounds of the claim cannot be determined.
Claim 140 is indefinite for the recitation of the term “[T]he method of claim 123, wherein the quality control composition according to claim 141 is in a medium corresponding to a medium of the test sample” such as recited in claim 140, lines 1-3 because instant claim 140 depends from claim 123, while claim 141 depends from claim 109. Additionally, instant claim 109 does not recite the presence of a “test sample,” such that the medium cannot correspond to a test sample. Moreover, claim 123 uses the quality control composition of claim 109, but does not recite the presence of a “medium” and, thus, the metes and bounds of the claim cannot be determined.
Response to Arguments
Applicant’s arguments filed December 16, 2025 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) the term “protection properties” is defined in the Specification and would be understood by one or skill in the art (Applicant Remarks, pg. 16, last partial paragraph, lines 4-11); (b) claim 111 has been amended to clarify that the properties are the same or “similar as” (paragraph [0016]) which is understood by one of ordinary skill (Applicant Remarks, pg. 16, last partial paragraph through pg. 17, first partial paragraph); and (c) regarding claim 116 and the term “the first protected nucleic acid” and “the second protected nucleic acid,” one of skill reading the claims in succession would understand what is meant by at least one first protected nucleic acid in claim 109 and "the" first protected nucleic acid in claim 116 as it is dependent on claim 109. Adding unnecessary terms to the claim such as "at least one" in every instance simply add more confusion to the claim than the current wording and makes the claims more cumbersome (Applicant Remarks, pg. 17, second full paragraph).
Regarding (a), regarding claim 111 and the “protection properties,” it is noted that claim 111 depends from instant claim 109, wherein claim 109 does not recite any nucleic acid sequence “protection properties,” processing through the NAT, any organism comprising the first target nucleic acid sequence and/or a recitation of what is to be tested for in a NAT. Thus, the claim remains rejected.
Regarding (b), regarding the term “similar to”, the Applicant is reminded that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26USPQ2d 1057 (Fed. Cir. 1993). It is noted that paragraph [0016] does not provide a definition for the term “similar to.” The term “similar to” is relative term that is not defined by the claim, and the Specification does not provide a standard for ascertaining the requisite amount of ‘similarity’ between protecting vehicle properties and an unidentified (and unrecited) organism to be tested for in a NAT. Thus, the claim remains rejected.
Regarding (c), regarding the rejection of claim 116, the Examiner is not persuaded by Applicant’s assertion that adding proper antecedent basis is unnecessary and/or that it makes the claims more cumbersome. The claims recite a multitude of different nucleic acid sequences (e.g., target nucleic acid sequence, a first target nucleic acid sequence, second target nucleic acid sequence, at least one protected nucleic acid sequence, at least one second protected nucleic acid sequence, a first nucleic acid sequence, a second nucleic acid sequence, a first protected nucleic acid sequence and/or second protected nucleic acid sequence, additional first protected nucleic acid sequence, three protected nucleic acid sequences, each first nucleic acid sequence, two first protected nucleic acid sequences, the second protected nucleic acid, etc.), such that proper antecedent basis is the only method of understanding and/or following which nucleic acid sequences are being referred to in each of the claims. Thus, the claim remains rejected.
Claim Rejections - 35 USC § 112(d)
The rejection of claim 140 is maintained, and claim 111 is newly rejected, under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Amended claim 111 recites: “that are same as or similar to an organism comprising the first target nucleic acid sequence the presence of which is to be tested for in the test article” in lines 4-6 because claim 111 depends from claim 109, wherein instant claim 109 does not recite the presence of “an organism” in the body of the claim. Additionally, the preamble of claim 109 recites the terms “a viable or pathogenic organism in a test article” and “a virus, a virus-like particle, a bacterium, a eukaryotic cell, or an inactivated, non-viable or non-pathogenic organism” but does not recite an organism to be tested for Thus, claim 109 is an improper dependent claim 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.
Amended claim 140 recites: “[T]he method of claim 123, wherein the quality control composition according to claim 141 is in a medium corresponding to a medium of the test sample” in lines 1-3 because instant amended claim 140 depends from claim 123 and recites claim 141, wherein claim 141 depends from claim 109. Moreover, claim 123 uses the quality control composition of claim 109, wherein claim 109 does not recite a “test sample” or a “medium;” and claim 123 does not recite the presence of a “medium.” Thus, claim 140 is an improper dependent claim 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 may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 101
The rejection of claims 109-111, 116, 123 and 140 is maintained, and claim 141 is newly rejected, under 35 U.S.C. 101 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. An analysis with respect to the claims as a whole reveals that they do not include additional elements that are sufficient to amount to significantly more than the judicial exception. See Alice Corp. Pty. Ltd. v. CLS Bank Int’l, 134 S. Ct. 2347, 110 U.S.P.Q.2d 1976 (2014); Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2116, 106 U.S.P.Q.2d 1972 (2013); Mayo Collaborative Svcs. v. Prometheus Laboratories, Inc., 132 S. Ct. 1289, 101 U.S.P.Q.2d 1961 (2012). See also 2014 Interim Guidance on Patent Subject Matter Eligibility, available at http://www.gpo.gov/fdsys/pkg/FR-2014-12-16/pdf/2014-29414.pdf (“2014 Interim Guidance”), and the Office’s examples to be considered in conjunction with the 2014 Interim Guidance in examination of nature-based products, available online at http://www.uspto.gov/patents/law/exam/mdc_ examples_nature-based_ products.pdf (“Nature-Based Products Examples”). See also; the 2019 Revised Patent Subject Matter Eligibility Guidance (hereinafter “2019 PEG”) published in January 2019. This rejection is proper. This rejection is proper.
Analysis of subject-matter eligibility under 35 U.S.C. § 101 requires consideration of three issues: (1) whether the claim is directed to one of the four categories recited in §101; (2) whether the claim recites or involves a judicial exception (i.e., a law of nature, natural phenomenon, or natural product); and (3) whether the claim as a whole recites something that amounts to significantly more than the judicial exception. In this case, the claims as a whole are directed to a natural phenomenon in the form of detecting the nucleic acids in a test sample and determining the presence and/or characteristic of an organism (e.g., infectiousness, transmission, virulence, ability to cause disease, etc.); and a natural product including naturally occurring nucleic acids in the form of a quality control composition, comprising: (a) at least one first protected nucleic acid sequence comprising a first nucleic acid sequence, which is characteristic of a first target nucleic acid sequence being tested in the NAT; and (b) at least one second protected nucleic acid sequence comprising a second nucleic acid sequence, which is characteristic of a first target nucleic acid sequence in the test article of a second target nucleic acid sequence being tested in the NAT, wherein the at least one first and at least one second protected nucleic acid sequences are in separate protecting vehicles; where each of the separate protecting vehicles are: (i) any enclosing substance or enclosing barrier, protecting the nucleic acid sequences by their containment within the protecting vehicles, wherein the separate protecting vehicles are independently selected from the group consisting of a virus, a virus like particle, a bacterium, a eukaryotic cell, a liposome or a nanoparticle; (ii) same or different types of protecting vehicle; and (iii) protective of the at least one first protected nucleic acid sequence and the at least one second protected nucleic acid sequences, respectively, so that the at least one first protected nucleic acid sequence and the at least one second protected nucleic acid sequences are capable of being recovered in a nucleic acid extraction step of the NAT; and wherein the second nucleic acid sequence of the at least one second protected nucleic acid sequence is an exogenous nucleic acid sequence not natively present in the protecting vehicle of the second protected nucleic acid sequence, wherein the quality control composition is useful to assess the functionality of the NAT, wherein the NAT detects at least one of the presence and/or characteristics of an organism to be tested for in a test article by detecting target nucleic acid sequences in the test article. Therefore, they must each be considered to determine whether, given their broadest reasonable interpretation, they amount to significantly more than the judicial exception.
The claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, claims 109-111, 116, 123, 140 and 141 do not recite something significantly different than the judicial exception. The rationale for this determination is explained below:
In the instant case, the claims are broadly directed to a quality control composition used to assess the functionality of a Nucleic Acid Test (NAT), wherein the NAT can be used to detect at least one of the presence and/or characteristics of an organism by detecting target nucleic acid sequences in a test article, the quality control composition comprising: (a) at least one first protected nucleic acid sequence comprising a first target nucleic acid sequence, which is characteristic of the presence in the test article of a first target nucleic acid sequence being tested in the NAT; and (b) at least one second protected nucleic acid sequence comprising a second target nucleic acid sequence, which is characteristic of a second nucleic acid sequence in the test article being tested in the NAT, wherein the at least one first and at least one second protected nucleic acid sequences are in separate protecting vehicles, wherein each of the separate protecting vehicles are: (i) any enclosing substance or enclosing barrier, protecting the nucleic acid sequences by their containment within the protecting vehicles, wherein the separate protecting vehicles are independently selected from the group consisting of a virus, a virus like particle, a bacterium, a eukaryotic cell, a liposome or a nanoparticle; (ii) same or different types of protecting vehicle; and (iii) protective of the at least one first protected nucleic acid sequence and the at least one second protected nucleic acid sequences, respectively, so that the at least one first protected nucleic acid sequence and the at least one second protected nucleic acid sequences are capable of being recovered in a nucleic acid extraction step of the NAT; and wherein the second nucleic acid sequence of the at least one second protected nucleic acid sequence is an exogenous nucleic acid sequence not natively present in the protecting vehicle of the second protected nucleic acid sequence.
Beginning with Step I of the analysis, which asks whether the claimed invention falls within a statutory category, such that the instant claims are directed to a process and a composition of matter, thus, the instant claims are directed to a statutory category. Step I: [YES].
Proceeding to Step IIA of the analysis, which asks if the claimed invention is directed to a judicial exception, such that claims 109-111, 116, 123, 140 and 141 are drawn to a judicial exception in the form of; (1) a natural phenomenon in the form of detecting naturally occurring nucleic acids in a test sample and determining the presence of and/or characteristic of the organism and/or nucleic acids (e.g., infectiousness, transmission, virulence, ability to cause disease, etc.); as well as, being directed to (2) naturally occurring products and/or non-naturally occurring products including naturally occurring organisms, nucleic acid sequences, and protecting vehicles; and/or non-naturally occurring nucleic acid sequences and/or protecting vehicles which do not possess markedly different characteristics such as different biological or pharmacological functions or activities, chemical or physical properties and/or structure/function and form as naturally occurring and/or non-naturally occurring organisms and/or nucleic acid sequences in a test article (e.g., an organism, cells, whole organism, food products, a biological sample, etc.) and/or in separate protecting vehicle (e.g., nanoparticles, liposomes, viruses, bacteria, biological samples, cells, the body of a patient, etc.). Thus, under the revised Step IIA analysis, the claims are directed to a naturally occurring products and/or non-naturally occurring products. Step IIA: [YES].
Step IIA - Prong One of the revised Step IIA analysis asks if the claims recite additional elements that integrate the judicial exception into a practical application of the exception. The claims are directed to a natural phenomenon and a quality control composition, comprising: (a) at least one first protected nucleic acid sequence comprising a first target nucleic acid sequence the presence of which is characteristic of a first target nucleic acid sequence in a test article being tested in the NAT, wherein the at least one first protected nucleic acid is in a protecting vehicle; and (b) at least one second protected nucleic sequence which is characteristic of a second target nucleic acid sequence in the test article being tested in the NAT, wherein the at least one second protected nucleic acid is in a protecting vehicle, the second nucleic acid sequence encoding a gene selected from the group consisting of an antibiotic resistance gene, a drug resistance gene, or a virus gene; wherein the at least one second protected nucleic acid is in a protecting vehicle second protected nucleic acid sequences are in separate protecting vehicles; wherein each of the separate protecting vehicles are: (i) any enclosing substance or enclosing barrier, wherein the separate protecting vehicles are independently selected from the group consisting of a virus, a virus-like particle, a bacterium, a eukaryotic cell, or an inactivated, non-viable or non-pathogenic organism; (ii) same or different types of protecting vehicles; and (iii) protective of the at least one first protected nucleic acid sequence and the at least one second protected nucleic acid sequence, wherein the at least one second protected nucleic acid sequence is an exogenous nucleic acid sequence not natively present in the second protecting vehicle.
It is noted that the specific composition, the NAT, the characteristics, the first protected nucleic acid sequence, the second protected nucleic acid sequence not natively present in its protecting vehicle, the test article, the sequence being tested in separate protecting vehicles are not provided in instant claim 109. Thus, the claims do not integrate the judicial exception into a practical application of the judicial exception. It is known that an inventive concept "cannot be furnished by the unpatentable law of nature (or natural phenomenon or abstract idea) itself." Genetic Techs. v. Merial LLC, 818 F.3d 1369, 1376, 118 USPQ2d 1541, 1546 (Fed. Cir. 2016). See also Alice Corp., 134 S. Ct. at 2355, 110 USPQ2d at 1981 (citing Mayo, 566 U.S. at 78, 101 USPQ2d at 1968 (after determining that a claim is directed to a judicial exception, "we then ask, ‘[w]hat else is there in the claims before us?"); RecogniCorp, LLC v. Nintendo Co., 855 F.3d 1322, 1327, 122 USPQ2d 1377 (Fed. Cir. 2017). The claims do not recite additional elements or a combination of elements beyond the judicial exception to apply, rely on, or use the judicial exception in a manner that imposes meaningful limits on the judicial exceptions. Thus, the claims do not integrate the judicial exception into a practical application of that exception. Step IIA: [NO].
Proceeding to Step IIB of the analysis: the question then becomes what element or what combination of elements is sufficient to amount to significantly more than the judicial exception? The instant independent claim is recited at a high level of generality, such that substantially all practical applications of the judicial exception are covered. For instance, the claims are recited without any specificity as to the specific composition; the functionality of the NAT; the method of assessing functionality; the organism; the protecting vehicles; the specific NAT; what is detected; the presence or absence of an organism; the specific characteristics of an organism; the number or type of organism; the target nucleic acids; the test article; the quality control composition; the at least one first nucleic acid sequence; the NAT conditions; the at least one second nucleic acid sequence; the exogenous nucleic acid sequences; the identities of the separate protecting vehicles; the associated substance or barrier; the container; the extraction steps; the method of obtaining; the method of providing; the method of performing the NAT; the method of comparing; and/or where the second nucleic acid sequence is non-natively present.
For example, non-viable particles (and in particular liposome particles, particles which are in the form of a viral protein coat, non-viable genetically modified organisms or particles made of synthetic polymers), comprising an internal control (IC) nucleic acid sequence as an internal control in nucleic acid-based analysis were known in the art, wherein the use of nucleic acid-based analysis in the field of diagnostic testing including for the diagnosis of microbiological pathogens and genetic disorders, the discovery of unknown infectious agents and improved diagnostic tools, wherein nucleic acid-based analysis can be either qualitative or quantitative and can involve nucleic acid-based amplification techniques, such that ideal IC sequence generally comprises a binding region, such as a primer or probe binding region which are substantially identical to the equivalent regions to the primers or probes bind in the target nucleic acid to be detected. Additionally, a NAT comprises the steps of: (i) obtaining a sample to be analyzed (obtaining a test sample); (ii) bringing said sample into contact with non-viable particles comprising an appropriate internal control nucleic acid; (iii) inducing the release of the nucleic acid to be analyzed from within the sample and the release of the internal control nucleic acid from within the non-viable particles (interpreted as a first protecting vehicle and a second protecting vehicle comprising exogenous and endogenous nucleic acids); and (iv) analyzing the released nucleic acids (performing the NAT), such that in step (i) the sample to be analyzed can be any sample on which it is desired to carry out a qualitative or quantitative nucleic acid-based assay (interpreted as a quality control composition), wherein said samples can thus be derived from in vitro sources (such as cultured cells, bacteria or viral particles) or in vivo sources (such as samples derived from human, plant or animal sources) (interpreted as eukaryotic cells as protecting vehicles) or synthesized in the case of samples containing non-naturally occurring target entities, such that other samples might be those that are tested for detection of food pathogens, wherein samples include blood, serum, plasma, saliva, feces, urine, milk and organ, tissue or cellular extracts or secretions, e.g. mucosa! secretions etc. as evidenced by Berg (US20110065092; Abstract; paragraphs [0003]; [0006]; and [0064]-[[0070]). Moreover, methods of detecting, quantifying, and identifying known or novel pathogens including influenza, hepatitis A, hepatitis B, Dengue, pneumonia using nucleic acid biochips including ViroChip, FluChip, BloodChip, and/or TickChip on commercially available platforms comprising a pan-viral microarray with 60,000 70-nt commercial probes which can tolerate several mismatches, which can be used for the discovery of viruses such as SARs coronavirus, Human cardioviruses and Avian bornaviruses in combination with next-generation sequencing on commercially available platforms such as Ion Torrent, Roche GS454 Jr., Pacific Biosciences, and Illumina MiSeq using barcoded primers, wherein the FluChip can detect exogenous viruses in humans including H1N1 and H2N2 subject present a variety of symptoms such as diarrhea, headache, sore throat, fever, chills, and cough are known in the art as evidenced by Chiu (Presentation, IPFA/PEI International Workshop, Budapest, Hungary, 2012, 1-43; of record; pgs. 1-10, 26 and 39); and it is known that exogenous viruses including cancer-associated viruses can be found to infect humans and animals as evidenced by Delwart (PLoS Pathogens, 2013, 9(2), 1-4; Abstract; and pg. 3, col 2); and endogenous retroviruses (ERVs) have contributed to more than 8% of the human genome, wherein viral RNA is permanently integrated into the nuclear DNA of the host cell as a provirus are known in the art as evidenced by Wildschutte (PNAS, 2016, 1-9; Abstract; and pg. 1, col 1, first full paragraph), wherein integration of a DNA copy of the viral genome into a host cell chromosome is an essential step in the retroviral replication cycle as evidenced by Craigie (Cold Springs Harbor Perspectives in Medicine, 2012, 1-18; pg. 1, col 1). Furthermore, performing spiked-in metagenomic experiments are known in the art including experiments comprising Neisseria meningitidis, S. agalactiae, and C. albicans obtained from the American Type Culture Collection that was subcultured and used with synthetic CSF; as well as, Mycobacterium fortuitum and Mycobacterium abscessus isolates derived from infected patients; and validation of metagenomic next-generation sequencing tests for pathogen detection is known in the art, wherein biological specimens can be analyzed for pathogens in human cells including three patient respiratory specimens positive for representative pathogens tested in triplicate from nucleic acid extraction, such that result were compared qualitatively; and that analytic sensitivity can be determined for a given pathogen (strain) at a given sequencing depth and (1) average specimen, (2) a representative control specimen, or (3) an individual specimen for which sufficient amounts of residual volumes are available as evidenced by Schlaberg et al. (Arch Pathol Lab Med, 2017, 141, 776-786; of record; pg. 778, col 2, last partial paragraph; pg. 779, col 1, first partial paragraph; pg. 779, col 2, last partial paragraph; pg. 780, col 1, first partial paragraph; and Example 1; and pg. 780, col 2, Example 1). Moreover, high throughput testing of biological samples that may or may not comprise microorganisms, and methods including the use of diagnostic multiplexing panel (DMP) specifically designed for simultaneous identification of a plurality of potential microorganisms that can be present in the biological sample via a primer extension reaction directed at highly conserved nucleic acid sequences in the microorganism is under test, wherein the biological sample is immobilized on a solid substrate at a first location before being transferred to a second location for analysis using the DMP for the diagnosis of infection pathogens; the method comprising immobilizing the biological sample; transferring the immobilized biological sample to a second location; performing a nucleic acid amplification step on microorganism DNA; combining target sequences with primer sequences including primers on a microarray; (e) performing a primer extension reaction; and analyzing the reaction product for target sequences including by mass spectrometry, DNA microarray, incorporation of fluorescently labeled nucleotides; as well as, infectious diseases including MRSA, SARS, avian fluid, HIV, malaria and other pathogens that cause death world-wide; as well as, viral, bacterial, fungal and protozoan microorganisms that are pathogenic to an animal host as evidenced by Semikhodskii et al. (US20160108467, published April 21, 2016; of record; Abstract; and paragraphs [0003]; [0011]-[0017]; [0023]; [0035]; and [0036]); and compositions and methods for the simultaneous multiplex detection of biomarkers in an environmental, non-biological or biological sample including multiple pathogens such as viruses, bacteria, fungi, protozoa and helminths present in a sample; and that test options for the presence of a microorganism including in a human host is shown in Figure 1A including antibody-bead capture, DNA-bead capture, PCR, immunoassay, DNA probe amplification, colony counting, and restriction digest mapping, wherein Figure 2 depicts the design of the PathoChip for metagenome 60 nt probes are selected for all viruses and selected human pathogenic microorganisms; and that cancer is associated with papillomavirus, hepatitis B or C, Epstein-Barr virus, human herpesvirus 8, and T-cell leukemia virus type 1), and one bacterium (Helicobacter pylori); as well as, nucleic acid amplification was known in the art as evidenced by Robertson et al. (US10883145, issued January 5, 2021; of record; effective filing date April 10, 2015; Abstract; col 1; and col 8, lines 28-43; and Figures 1A and 2A-B). Step IIB: [NO].
In sum, when the relevant factors are analyzed, the claims as a whole do NOT recite additional elements that amount to significantly more than the judicial exception itself. Accordingly, claims 109 and 123 DO NOT qualify as eligible subject matter.
Dependent claim(s) 110, 111, 116, 140 and 141 when analyzed as a whole are held to be patent ineligible under 35 U.S.C. 101 because they do not add anything that makes the natural product in claim 109 significantly different. For example, claim 116 encompasses the method of claim 109, wherein the quality control composition further comprises an additional first protected nucleic acid sequence, but it does not add anything that makes the natural product in claim 109 significantly different.
Thus, the claims as a whole do NOT recite additional elements that amount to significantly more than the judicial exception itself.
In light of the above consideration and the new guidance, claims 109-111, 116, 123, 140 and 141 are non-statutory. This rejection is newly recited as necessitated by the new Guidance set forth in the Memorandum of July 30, 2015 updating the June 25, 2014 guidance (see June 25, 2014 memorandum from Deputy Commissioner for Patent Examination Policy Andrew Hirshfeld titled Preliminary Examination Instructions in view of the Supreme Court Decision in Alice Corporation Pty. Ltd. v. CLS Bank International, et al. (Alice Corp. Preliminary Examination Instructions) and the Revised Patent Subject Matter Eligibility Guidance (See, Federal Register, vol. 84, No. 4, January 7, 2019).
Response to Arguments
Applicant’s arguments filed December 16, 2025 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) the claims are not directed to natural products; that claim 109 specifies that the composition comprises at least two separate nucleic acid sequences that are within two separate protecting vehicles mixed together in combination (see e.g., Figure 3); and the second protecting vehicle contains an exogenous nucleic acid sequence non-native to the protecting vehicle, such as an antibiotic resistance gene, a drug resistance gene, or a virus gene and the protecting vehicle is manipulated by one of skill in the art to include the nonnative, exogenous nucleic acid sequence. There is no evidence for this in nature (Applicant Remarks, pg. 18, last full paragraph, and last partial paragraph through pg. 19, first partial paragraph); (b) the claims are directed to a practical application of any judicial exception including as a quality control composition that comprises multiple different elements in a combination useful as a control in a nucleic acid test, which is a discrete, useful application of the judicial exception, where MPEP §2106 states that claims taken as a whole (emphasis added) that fall within a statutory category; and the composition provides significantly more than the judicial exception (Applicant Remarks, pg. 19, last full paragraph through pg. 20, last full paragraph; and pg. 21, last full paragraph); and (c) none of the references cited provide a quality control composition; and one of the advantages of the present invention is the ability to mix and match first and second protected nucleic acids to provide consumers with the quality control composition to assess the specific NAT used by the consumers (Applicant Remarks, pg. 20, last partial paragraph through pg. 21, first full paragraph).
Regarding (a), as noted supra, although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26USPQ2d 1057 (Fed. Cir. 1993), include what is provided in Figure 3 of the Specification. Applicant’s assertion that the claims are not directed to natural products because claim 109 specifies that the composition comprises at least two separate nucleic acid sequences that are within two separate protecting vehicles mixed together in combination (see e.g., Figure 3); and the second protecting vehicle contains an exogenous nucleic acid sequence non-native to the protecting vehicle, such as an antibiotic resistance gene, a drug resistance gene, or a virus gene and the protecting vehicle is manipulated by one of skill in the art to include the nonnative, exogenous nucleic acid sequence. There is no evidence for this in nature, is not found persuasive. As an initial matter, instant claim 109 does not recite what Applicant asserts including: (i) protecting vehicles that are mixed together in combination; and/or (ii) protecting vehicles that have been manipulated by one of skill in the art to comprise an exogenous nucleic acid sequence. It is noted that human and/or livestock cells can be infected with methicillin-resistant Staphylococcus aureus (MRSA), which is caused by the presence of the mecA gene, wherein the mecA gene encodes the 78-kDa penicillin-binding protein as evidenced by Deurenberg (pg. 223, col 1, first partial paragraph); and Matuszewska (Abstract; pg. 2, first full paragraph). Thus, naturally infected human & mammalian cells comprising MRSA are eukaryotic cells (protecting vehicles) comprising exogenous nucleic acid sequences not natively present in the protecting vehicle, which comprise a sequence encoding an antibiotic resistance gene. Moreover, human & animal cells infected with MSRA and/or methicillin-susceptible Staphylococcus aureus (MSSA) can be detected using a NAT as evidenced by Liu (Abstract). Thus, there are innumerable examples in nature where nucleic acid sequences are contained in protecting vehicles, including nucleic acid sequences that encode for an antibiotic resistance gene, a drug resistance gene, or a virus gene as recited in claims 109 and 123 (e.g., eukaryotic cells infected with tuberculosis, HIV, HPV, drug-resistant gonorrhea, SARS, smallpox, Candida auris, Clostridioides difficile, soil bacteria such as Streptomyces spp., Lactobacillus species, Lactococcus species, as well as, viroids, virions, influenza virus, exosomes, etc.), which include naturally occurring organisms, nucleic acid sequences, and protecting vehicles; and/or non-naturally occurring nucleic acid sequences and/or protecting vehicles which do not possess markedly different characteristics such as different biological or pharmacological functions or activities, chemical or physical properties and/or structure/function and form as naturally occurring and/or non-naturally occurring organisms and/or nucleic acid sequences in a test article (e.g., an organism, cells, whole organism, food products, a biological sample, etc.).
Regarding (b), Applicant’s assertion that the claims are directed to a practical application of any judicial exception including as a quality control composition that comprises multiple different elements in a combination useful as a control in a nucleic acid test, and the present composition provides significantly more than the judicial exception, is not found persuasive. Please see the 35 USC 112(b) rejection regarding instant claim 123 and that the method is indefinite with respect to how comparing disparate results assesses a specific functionality common to all possible nucleic acid tests (NATs). Instant claim 109 is recited without any specificity regarding the functionality being assessed, the at least one first protected nucleic acid, the at least one second protected nucleic acid, what gene the nucleic acid encodes for, the identity of the protecting vehicles, the identity of any specific detector, laboratory equipment, etc. Additionally, instant claim 123 provides no specific method of obtaining, no specific test sample, organism, target nucleic acid sequence, NAT performed, the reaction conditions, the sensitivity without an extraction, the amount of amplification, the identity of a specific detector, whether the test sample NAT uses the same protecting vehicles, etc. as the quality control composition NAT, the identity of what is detected, the results produced, there is no specific quality control composition detected including nucleic acids, organism, no specific method of comparing (e.g., fluorescent signals, sequence fragments, computer implemented comparing, mathematical comparing, isolated product, etc.), the specific functionality assessed, and/or how comparing the NAT of a test sample (nucleic acid or organism) to the NAT of the quality control composition (nucleic acids within a protecting vehicle) assess any specific functionality of a NAT. There is absolutely no recitation regarding how the compared results assess a single functionality of a particular NAT using the method as recited. One of ordinary skill in the art could not use the quality control compositions encompassed by claim 109 in the method as recited in claim 123 to assess a single specific functionality of a NAT. Thus, the claims are not directed to a practical application of the judicial exception; and they do not provide significantly more than the judicial exception. The components of the quality control composition and the steps of the method as recited in instant claims 109 and 123 are well-known, purely convention or routine in the art.
Regarding (c), Applicant’s assertion that none of the references cited provide a quality control composition; and one of the advantages of the present invention is the ability to mix and match first and second protected nucleic acids to provide consumers with the quality control composition to assess the specific NAT used by the consumers, is not found persuasive. As an initial matter, instant claims 109 and 123 do not recite mixing and matching first and second protected nucleic acids, consumers, and/or assessing a specific NAT. Thus, the claims do not recite any of the advantages asserted by Applicant.
Regarding the references cited, the Examiner respectfully points out that each infected eukaryotic cell (either human or animal) represents a protecting vehicle comprising exogenous nucleic acids from a virus and/or bacterium often including nucleic acids that encode for an antibiotic resistant gene, a drug resistant gene, or a virus gene (e.g., a quality control composition). Berg clearly teaches the use of internal control (IC) nucleic acids contained or encapsulated within non-viable particles, where such non-viable particles are in the form of liposomes, protein coats or non-viable genetically modified organisms, which can be designed based on the particular target nucleic acid that is to be analyzed; and the use of nucleic acid-based analysis in the field of diagnostic testing including for the diagnosis of microbiological pathogens and genetic disorders, the discovery of unknown infectious agents and improved diagnostic tools, wherein nucleic acid-based analysis can be either qualitative or quantitative and can involve nucleic acid-based amplification techniques. Chiu teaches biological samples comprising a plurality of human cells as protecting vehicles that contain human nucleic acids and exogenous nucleic acids including nucleic acids encoding for a viral gene and antibiotic resistance (e.g., SARS, H1N1, H3N2, H2N2, HIV-1, flu, etc.), which are characterized by various analyses methods including PCR; tested on platforms such as Ion Torrent, Roche, Illumina, etc.; the data are analyzed, sequences are aligned, unmatched sequences are aligned to the GenBank, signatures are produced and compared, and viral pathogens are identified, such that the functionality of the NAT is assessed. Thus, Chiu clearly teaches the quality control composition recited in claim 109, which is tested in a NAT as recited in claim 123. Moreover, Semikhodskii teaches human biological samples that are subjected to PCR, immunoassay, etc. including for the detection and/or identification of CMV, HIV, HBV, MRSA, SARS, etc., where the eukaryotic cells are a plurality of the same protecting vehicles comprising human nucleic acids and exogenous nucleic acids including nucleic acids encoding for antibiotic resistance genes, viral genes, and/or drug resistance genes, where sequences are amplified and compared to target sequences, such that the functionality of the NAT has been assessed. Thus, the claims remain rejected.
Claim Rejections - 35 USC § 102
The rejection of claims 109-111, 116, 123 and 140 is maintained, and claim 141 is newly rejected, under 35 U.S.C. 102(a1)/(a2) as being anticipated by Semikhodskii et al. (US Patent Application Publication 20160108467, April 21, 2016; of record) as evidenced by Krupp et al. (hereinafter “Krupp”) (Indian Journal of Sexually Transmitted Diseases and AIDS, 2015, 36(1), 1-6); and CDC (CDC, 2024,
1-2).
Regarding claims 109-111, 116, 123, 140 and 141, Semikhodskii et al. teach that methods include the use of a diagnostic multiplexing panel (DMP) specifically designed for the simultaneous identification of a plurality of potential microorganisms that can be present in the biological sample via a primer extension reaction directed a highly conserved nucleic acid sequences in the microorganisms under test, wherein the biological sample is typically immobilized on a solid substrate at a first location before being transferred to a second location for analysis using the DMP, wherein the method is particularly suited to diagnosis of the presence of infectious pathogens in the biological sample (interpreting microorganisms as organism; a biological sample as a test sample/test article; interpreting conserved nucleic acids as first target nucleic acid, and/or second target nucleic acids that are exogenous and non-native to the patient; primer extension as a second target nucleic acid non-native and exogenous to the first target nucleic acid sample; obtaining a test sample; and interpreting steps (a) and (b) in parallel or in sequence, claims 109 and 123) (Abstract). Semikhodskii et al. teach that in an asymptomatic host, it is often difficult to decide which microorganism the patient should be tested for, because negative results for two or three infectious organisms can provide a false sense of security (interpreted as two or three organisms, claim 116) (paragraph [0007]). Semikhodskii et al. teach that Figure 1 is a schematic representation of highly conserved DNA consensus sequences generated by comparison of several strains of the same species, the locations at which primers for the amplification or primer extension reaction are selected for use in a DMP of the invention are shown (interpreted as comparing the result of the NAT for a test article with the NAT for the quality control composition; and interpreting conserved consensus sequences as second target nucleic acid sequence is characteristic of members of the same species or genus of an organism, claims 109, 111 and 123) (paragraph [0021]). Semikhodskii et al. teach that the solid substrate of the invention is suitably selected from an absorbent fibrous material impregnated with one or more reagents that act to immobilize and inactivate any microorganisms present in the biological sample, or even to cause immobilization of nucleic acids contained within the microorganism (interpreted as two or three microorganisms; the substrate including fibrous material as protecting vehicles and/or test article; and reagents as inactivation using chemicals, claims 109, 123 and 130) (paragraph [0025]). Semikhodskii et al. teach that after the sample is deposited on the testing surface, the sealable chamber can be closed such that it encapsulates and protects the testing surface from further interferences or contamination (interpreting the sealable chamber as a protecting vehicle, claims 109 and 123) (paragraph [0027]). Semikhodskii et al. teach high throughput diagnostic testing of one or more biological samples for the presence of microorganisms in the sample, wherein the DMP provides a combination of primers that each specifically hybridize with a highly conserved sequences in DNA that is isolated from microorganisms that can be present within the biological sample; and that bacterial pathogens include Mycoplasma spp.; Chlamydia spp.; Ureaplasma spp; Neisseria spp.; Gardnerella spp.; Trichomonas spp.; Treponema spp; or the yeast Candida albicans; or viral pathogens such as: cytomegalovirus (CMV); hepatitis viruses (e.g. HAV, HBV, HCV, etc.); hepatitis E virus (HEV); hepatitis G and GB virus (GBY-C); human immunodeficiency viruses (HIV, HIV-1 , HIV-2); human papilloma viruses (HPV); herpes simplex viruses (HSV, HSV-1, HSV-2); Molluscum contagiosum virus (MCV); influenza virus; Epstein-Barr virus (EBV) and varicella-zoster virus (VZV) (interpreting biological samples and/or microorganisms as test articles; interpreting viruses and bacterium as protecting vehicles that protect nucleic acid sequences; first and second target nucleic acid sequences; first and second protected nucleic acid sequences; sequences of different organisms are exogenous of other protecting vehicles (viruses, bacteria, etc.); and same or similar sequence protection properties when processed through the NAT as an organism comprising the target nucleic acid sequence to be tested for, claims 109, 110, 111, 113 and 123) (paragraph [0032]). Semikhodskii et al. teach that the invention can provide information about the progression of some diseases by determining the concentration of detected pathogens, which in many cases reflects the progress of the disease, wherein concentration can include an assessment of viral load, such that quantitative information can be obtained from the primer extension phase of the reaction including by inclusion of a competitor sequence to a given target sequence, which competitor sequence contains an introduced polymorphism at a specified position in its sequence compared to the target sequence, and can serve as a benchmark for quantifying concentration of the polymorphism-containing target sequence from the microorganism of interest; and that inclusion of competitor sequences provides an internal control for all the enzymatic steps in the diagnostic method of the invention, wherein one or more control sequences comprise a sequence of DNA selected from a species unrelated to that of the biological sample, a species unrelated to the microorganisms being tested for, or a synthetic DNA sequence (interpreted as comparing the result of the NAT for a test article with the NAT for the quality control composition; and interpreting DNA of unrelated species, control sequences, synthetic DNA, etc. as second target nucleic acid sequence is characteristic of members of the same species or genus of an organism; exogenous to the genomic nucleic acid of the protecting vehicle; and same or different protecting vehicle, claims 109, 111, 113 and 123) (paragraph [0034]). Semikhodskii et al. teach that the DMP is suitably provided as a plurality of appropriately plexed primers in solution, and the DMP can also comprise primers that are immobilized on a solid surface such as in the form of a microarray, or a silicon substrate or glass surface (interpreted as a second target nucleic acid sequence; interpreting primers at specific locations on a solid surface to be protecting vehicles; sequence of the primers is exogenous of the protecting vehicle; and interpreting the solution as a medium, claims 109 and 123) (paragraph [0035]). Semikhodskii et al. teach that an aliquot of known good quality DNA diluted 1:1 with eluant obtained after extracting samples; and that for all the samples, good quality PCR products and mass spectrum was obtained (data not presented), which indicates that the chosen extraction method and washing protocol are adequate for MALDI-TOF analysis and also show that substances in human urine (interpreting dilution solution, extraction solution, urine, and mass spectra solutions as a medium of the test article, claims 140 and 141) (paragraph [0079]). Semikhodskii et al. teach detecting individual pathogens from a pathogen mixture three positive controls obtained by mixing sexually transmitted pathogens obtained from the NCTC were created using urine as a medium (interpreting urine as a medium corresponding to a medium of the test article, claims 140 and 141) (paragraph [0086]). Semikhodskii et al. teaches employing assays such as SpectroCHIP, genotyping, nucleic acid amplification including PCR, LCR, strand displacement amplification, transcription mediated amplification, and sequence-based amplification assay; MALD-TOF, etc. (interpreted as NAT, claims 109 and 123) (paragraphs [0008]; [0014]; [0075]; and [0079]). Semikhodskii et al. teaches that 44 samples were obtained from patients, DNA was extracted, and all samples were analyzed in the Sexually Transmitted Infection Multiplex Panel (STIMP)/Diagnostic Multiplex Panel (DMP) method using conventional DNA-based detection techniques and analyzed for the following microorganisms: Candida albicans, Chlamydia trachomatis, Gardnerella vaginalis, Mycoplasma genitalium, Mycoplasma hominis, Neisseria gonorrhoeae, Trichomonas vaginalis, Treponema pallidum, and Ureaplasma urealyticum; wherein a variety of cell lines were used as positive controls (interpreted as performing a NAT; interpreting Mycoplasma genitalium, Neisseria gonorrhoeae and Trichomonas vaginalis as encoding antibiotic resistance gene; detecting target nucleic acid sequence or organism in the NAT; and assessing the functionality of the NAT, claims 109 and 123) (paragraphs [0049]-[0051]; [0053]; and [0056]-[0057]); wherein it is known that Gonorrhea has developed resistance to nearly all antibiotics used for its treatment as evidenced by CDC (pg. 1, first full paragraph); and wherein tetracycline-resistant Neisseria gonorrhea was first reported in 1980’s, and ciprofloxacin-resistance in the early 2000s, such that in 2012, 33.4% of sampled isolates were resistant to penicillin, tetracycline, ciprofloxacin, or some combination of these; 1% were cefixime‑resistant; 14.7% ciprofloxacin‑resistant; and 0.3% azithromycin‑resistant, wherein growing antimicrobial resistance has also been observed in syphilis; Chlamydia trachomatis; Trichomonas vaginalis; Haemophilus ducreyi; and Mycoplasma genitalium as evidenced by Krupp (pg. 3, Introduction).
Semikhodskii et al. meets all the limitations of the claims and, therefore, anticipates the claimed invention.
Response to Arguments
Applicant’s arguments filed December 16, 2025 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) Semikhodskii does not disclose or suggest a quality control composition comprising both a first and second protected nucleic acid each within a separate protecting vehicle that is a bacterium, virus or virus-like particle. The DMP is not an organism or a protecting vehicle, the quality control composition does not comprise primers, and a sample from a patient is clearly NOT a quality control composition (Applicant Remarks, pg. 23); (b) the Examiner mistakenly equates a test sample in Semikhodskii with a quality control composition (Applicant Remarks, pg. 23, last full paragraph); (c) the specification defines a biological sample in paragraph [0130] as relating to a sample to be tested in a NAT, and can include the test article, and defines the protecting vehicle as an enclosing substance that inhibits the loss or degradation of nucleic acid sequence in the NAT up to the nucleic acid extraction process (paragraph [0134]), thus they are not interchangeable elements (Applicant Remarks, pg. 24, first full paragraph); and (d) the claimed elements are not disclosed in Semikhodskii as they are arranged in the claims (Applicant Remarks, pg. 24, second full paragraph).
Regarding (a), (b) and (d), as an initial matter, the Examiner has never suggested that DMP is an organism or a protecting vehicle. As noted in MPEP 2112.01(I),
where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Applicant’s assertion that Semikhodskii does not disclose or suggest a quality control composition comprising both a first and second protected nucleic acid each within a separate protecting vehicle that is a bacterium, virus or virus-like particle; the Examiner mistakenly equates a test sample in Semikhodskii with a quality control composition; and the claimed elements are not disclosed in Semikhodskii as they are arranged in the claims, is not found persuasive. Instant claim 109 is very broadly recited, wherein claim 109 clearly recites the components of a quality control composition. Any composition comprising the recited components is, therefore, a “quality control composition” according to instant claim 109. Additionally, instant claims 109 and 123 recite the term “comprising,” which is open-ended and does not exclude additional, unrecited elements or method steps, including protecting vehicles, primers, nucleic acids, additional assays, etc. Additionally -
Semikhodskii teaches:
A biological sample from a human that is tested for the presence of an infection, infectious pathogen and/or a mixture of infectious pathogens including one or more of: Mycoplasma spp.; Chlamydia spp.; Ureaplasma spp; Neisseria spp.; Gardnerella spp.; Trichomonas spp.; Treponema spp; or the yeast Candida albicans; MRSA, SARS, avian flu, malaria, cytomegalovirus (CMV); hepatitis viruses (e.g. HAV, HBV, HCV, etc.); hepatitis E virus (HEV); hepatitis G and GB virus (GBY-C); human immunodeficiency viruses (HIV, HIV-1, HIV-2); human papilloma viruses (HPV); herpes simplex viruses (HSV, HSV-1, HSV-2); Molluscum contagiosum virus (MCV); influenza virus; Epstein-Barr virus (EBV) and varicella-zoster virus (VZV) (where viruses such as SARAS include nucleic acids that encode for a viral gene; and bacteria such as MRSA and malaria comprise nucleic acids that encode for antibiotic resistance gene).
Thus, the cells in the human biological sample correspond to the eukaryotic cells recited in claim 109, which represent a plurality of same type protecting vehicles comprising human nucleic acids and exogenous nucleic acids; as well as, encoding for viral genes from the one or more virus and/or bacteria within the cells as disclosed by Semikhodskii. Semikhodskii also teaches:
Employing DNA based assays such as SpectroCHIP, genotyping, PCR, LCR, strand displacement amplification, transcription mediated amplification, sequence-based amplification assay, MALD-TOF, etc. (interpreted as NATs).
That 44 samples were obtained from patients, DNA was extracted, and all samples were analyzed in the Sexually Transmitted Infection Multiplex Panel (STIMP)/Diagnostic Multiplex Panel (DMP) method using conventional DNA-based detection techniques and analyzed for the following microorganisms: Candida albicans, Chlamydia trachomatis, Gardnerella vaginalis, Mycoplasma genitalium, Mycoplasma hominis, Neisseria gonorrhoeae, Trichomonas vaginalis, Treponema pallidum, and Ureaplasma urealyticum; wherein Neisseria gonorrhoeae cell lines were used as positive controls; wherein it is known that Gonorrhea has developed resistance to nearly all antibiotics used for its treatment as evidenced by CDC; and wherein it is known that tetracycline-resistant Neisseria gonorrhea was first reported in 1980’s, and ciprofloxacin-resistance in the early 2000s, such that in 2012, 33.4% of sampled isolates were resistant to penicillin, tetracycline, ciprofloxacin, or some combination of these; 1% were cefixime‑resistant; 14.7% ciprofloxacin‑resistant; and 0.3% azithromycin‑resistant, wherein growing antimicrobial resistance has also been observed in syphilis; Chlamydia trachomatis; Trichomonas vaginalis; Haemophilus ducreyi; and Mycoplasma genitalium as evidenced by Krupp (interpreted as performing a NAT; detecting target nucleic acid sequence or organism in the NAT; interpreting Mycoplasma genitalium, Neisseria gonorrhoeae and Trichomonas vaginalis as encoding antibiotic resistance gene; and assessing the functionality of the NAT).
Therefore, Semikhodskii teaches the quality control composition as recited in claim 109 and the method as recited in claim 123 including as they are arranged in the claims.
Regarding (c), Applicant’s assertion that the specification defines a biological sample in paragraph [0130] as relating to a sample to be tested in a NAT, and can include the test article, and defines the protecting vehicle as an enclosing substance that inhibits the loss or degradation of nucleic acid sequence in the NAT up to the nucleic acid extraction process (paragraph [0134]), thus they are not interchangeable elements, is not found persuasive. Please see the discussion supra wherein although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims, what is recited only in the preamble of claim 109, and recitation of the term “comprising” in claims 109 and 123. Applicant’s argument regarding a sample to be tested, a test article, and a protecting vehicle is unclear to the Examiner. Instant claim 109 is directed to a product; and instant claim 123 is directed to a process that uses the product of claim 109. Semikhodskii clearly teaches all of the limitations of the claims and, therefore, anticipates the claimed invention.
The rejection of claims 109-111, 116, 123, and 140 is maintained, and claim 141 is newly rejected, under 35 U.S.C. 102(a1)/102(a2) as being anticipated by Berg et. al. (hereinafter “Berg”) (US Patent Application Publication 20110065092, published March 17, 2011).
Regarding claims 109-111 and 116, Berg teaches non-viable particles (and in particular liposome particles, particles which are in the form of a viral protein coat, non-viable genetically modified organisms or particles made of synthetic polymers), comprising an internal control (IC) nucleic acid sequence as an internal control in nucleic acid-based analysis (interpreted as protecting vehicles modified to be non-viable including liposomes and particles including virus-like particles; comprising a sequence that is exogenous to a nucleic acid sequence of the protecting vehicle; and comprising an IC for a quality control composition, claims 109, 110, 113, 123 and 130) (Abstract). Berg teaches that false positive results can be caused by contamination between different samples or by contamination of the sample with previously made amplification products, also called "carry-over" contamination. Much research and development has been undertaken to find ways to reduce the risk for "carry-over" contamination, wherein it is preferred that the IC nucleic acid (or at least a significant proportion of the IC nucleic acid) be encapsulated within the particles as described above as any nucleic acid located on the external surface of the particle will be at risk of degradation, e.g. by nuclease enzymes or contamination by inhibitory impurities which may be present in the sample (paragraphs [0004]; and [0017]). Berg teaches that an ideal IC sequence generally comprises a binding region, such as a primer or probe binding region which are substantially identical to the equivalent regions to the primers or probes bind in the target nucleic acid to be detected (interpreted as a first protecting vehicle comprising endogenous nucleic acid sequence; and comprises a sequence characteristic of the presence of the test article of a first target nucleic acid sequence, claims 109, 116 and 123) (paragraph [0006], lines 12-16). Berg teaches the use of nucleic acid-based analysis in the field of diagnostic testing including for the diagnosis of microbiological pathogens and genetic disorders, the discovery of unknown infectious agents and improved diagnostic tools, wherein nucleic acid-based analysis can be either qualitative or quantitative and can involve nucleic acid-based amplification techniques (interpreted as nucleic acid testing (NAT or NAAT), claims 109, 116 and 123) (paragraph [0003], lines 1-11). Berg teaches the use of IC nucleic acids contained or encapsulated within non-viable particles in this way and in particular those contained within liposomes or protein coats have advantages over the use of viable genetically modified organisms, which have been used previously as internal controls (interpreted as protecting vehicles modified to be non-viable including liposomes and particles including virus-like particles; and comprising an IC for a quality control composition, claims 109, 110, 123 and 130) (paragraph [0011], lines 1-5). Berg teaches that liposomes or protein coats containing IC nucleic acids are inexpensive to design and adapt to any nucleic acid amplification/detection system or any other non-amplification based nucleic acid assay and it is less laborious (and therefore less expensive) to make different kinds of liposomes or protein coats with regard to sequence and particle properties, wherein the non-viable particles in the form of liposomes, protein coats or non-viable genetically modified organisms are biologically safe, politically non-controversial, and contain no potential endogenous or exogenous hazardous sequences such as antibiotic resistance genes (interpreted as having the same or different types of protecting vehicles; separate protecting vehicles; the presence or characteristic of a nucleic acid sequence; comprises nucleic acid protection properties; and interpreting modified organisms to be protective vehicles comprising exogenous nucleic acids not natively present in the protecting vehicle, claims 109-111 and 123) (paragraph [0011], lines 6-17). Berg teaches that by using an IC nucleic acid which has been encapsulated in a non-viable particle in accordance with the present invention, the IC nucleic acid can be added to the samples at a very early time point in the process, i.e. such particles can even be added to the urine, blood, etc. directly after the sample has been derived from the patient (i.e. at the collection step) and before transportation and/or subsequent processing to release nucleic acid takes place (interpreting blood and urine samples to comprise cells interpreted to be a first protecting vehicle comprising endogenous nucleic acids; comprising a sequence characteristic of a test article or organism; and having protection characteristics, claims 109 and 123) (paragraph [0013], lines 1-8). Berg teaches that the stage at which the particular type of non-viable particle is added to the sample will depend on the intention of the use of the internal control, e.g. as reference standard in quantitative analysis as a quality control for the lysis of the cells in the sample, as a quality control for the detection step, etc.), such that in a conventional IC is in the form of DNA or RNA which was not encapsulated would not necessarily be added at such an early time point as there is a significant risk that the samples will contain enzymes or other impurities (e.g. RNAase or DNAase enzymes) which will degrade the IC DNA/RNA while not degrading the target nucleic acid because it is not exposed to these elements (it is still within the cells present in the collected sample), wherein in such a case, the IC sequence would fail to work as a quality control; while the non-viable particles protect the IC nucleic acid at this early stage (like a cell membrane) with the IC nucleic acid only being released when the target nucleic acid was also released (interpreted as a quality control composition having a protective effect; a target sequence; interpreting a target nucleic acid as an endogenous or native nucleic acid in a first protection vehicle; and having a characteristic of an organism to be tested for, claims 109, 111 and 123) (paragraph [0013], lines 9-26). Berg teaches that the term “non-viable particle” refers to any entity which is capable of encapsulating, entrapping or embedding an internal control nucleic acid but which is not capable of propagation either alone (i.e. by self-propagation) or by culture in a biological system which would normally allow the propagation of the entity in question, wherein such particles may never have been capable of being propagated, e.g. liposomes, protein particles, or synthetic particles or other particles which consist solely of an encapsulating shell and do not contain any genetic material which enables replication and propagation of the particle in a biological system, for example particles which are made up of viral coat proteins or viral capsid proteins, wherein other “non-viable particles” included herein are those capable of being propagated, e.g. virus particles or other pathogenic organisms, but which have been altered in such a way that replication and/or propagation of the particles are no longer possible (interpreted as a first protecting vehicle and a second protecting vehicle that are separate; comprising exogenous nucleic acids; vehicles including liposomes, virus-like particles, nanoparticles, and virus or bacteria; and comprising sequence protection properties when processes through the NAT, claims 109, 111 and 123) (paragraph [0035]). Berg teaches that the non-viable particles can be designed to include proteins which are naturally found in the membrane of the target cells, wherein the inclusion of such proteins will enable the particles to more closely mimic the target cell but can also be used in order to target the delivery of a liposome, wherein it is important that the non-viable particles used for a particular assay mimic as far as possible the target cells or viruses which contain the target nucleic acid (interpreted as a protecting vehicle of the first nucleic acid sequence is a representative strain, species, or genius of an organism to be tested for in the test article by the NAT; and comprising native genomic nucleic acid sequence, claim 111) (paragraphs [0038]; and [0040], lines 1-4). Berg teaches procedures comprising contamination control – liposomes prepared without DNA (paragraph [0091]). Berg teaches that liposomes encapsulating and internal control (IC) nucleic acid were prepared as described in Example 1; DNA was isolated from an in vivo sample containing C. Trachomatis spiked with entrapped IC, wherein a cell suspension of a cultured C. trachomatis L2 strain was spiked with liposomes/IC DNA complex was prepared as described above; and Chlamydia and IC DNA was prepared from the cells/liposomes, wherein the purified Chlamydia and IC DNA was analyzed in a multiplex PCR using primer sets (interpreting the entrapped IC and bacterial cell suspensions as two or more protecting vehicles and protected nucleic acid sequences; and performing a NAT, claims 109 and 123) (paragraphs [0107]-[0109]).
Regarding claim 123, Berg teaches that the method of nucleic acid-based analysis according to the present invention will comprise the steps of: (i) obtaining a sample to be analyzed (obtaining a test sample); (ii) bringing said sample into contact with non-viable particles comprising an appropriate internal control nucleic acid; (iii) inducing the release of the nucleic acid to be analyzed from within the sample and the release of the internal control nucleic acid from within the non-viable particles (interpreted as a first protecting vehicle and a second protecting vehicle comprising exogenous and endogenous nucleic acids); and (iv) analyzing the released nucleic acids (performing the NAT), such that in step (i) the sample to be analyzed can be any sample on which it is desired to carry out a qualitative or quantitative nucleic acid-based assay (interpreted as a quality control composition), wherein said samples can thus be derived from in vitro sources (such as cultured cells, bacteria or viral particles) or in vivo sources (such as samples derived from human, plant or animal sources) (interpreted as eukaryotic cells as protecting vehicles) or synthesized in the case of samples containing non-naturally occurring target entities, such that other samples might be those that are tested for detection of food pathogens, wherein samples include blood, serum, plasma, saliva, feces, urine, milk and organ, tissue or cellular extracts or secretions, e.g. mucosa! secretions etc. (interpreted as eukaryotic cells as protecting vehicles; and endogenous and exogenous nucleic acid sequences in different protecting vehicles, claims 109 and 123) (paragraph [0064]-[[0070]). Berg teaches that samples are obtained from patients, which can optionally involve the steps of transporting the sample to the analysis laboratory for storage of the sample prior to preparation, which can occur after step (i), step (ii) or steps (iii) (interpreted as obtaining a sample, claim 123) (paragraph [0076]). Berg teaches that Example 4 demonstrates the preparation of liposomes and encapsulation of the IC nucleic acid; the lysis of liposome/DNA complex, analysis of the isolated DNA from the liposomes, which was amplified by PCR, wherein PCR primers used in the assay are for the detection of Chlamydia trachomatis including nucleic acids encapsulated in POPC/DDAB liposomes, such that PCR analysis of the DNA solution including purified Chlamydia and IC DNA were analyzed in multiplex PCR using the primer sets; as well as, comparing the results of Example 4 with liposomes prepared in Example 6 (interpreted as obtaining a test sample, providing a quality control composition; performing a NAT; and comparing results, claim 123) (paragraphs [0114]-[0124]).
Regarding claims 140 and 141, Berg teaches that the sample to be analyzed is likely to be in the form of a solution or can conveniently be made in the form of a solution (interpreted as the composition comprising a medium, claims 140 and 141) (paragraph [0071], lines 3-4). Berg teaches that the appropriate lysis medium/buffers are well known and standard in the art and can for example contain detergents or proteinases or protein denaturing agents such as guanidine thiocyanate which will disrupt the membranes of the target cells or viruses (and the liposome membranes) and also the particles which comprise a viral protein coat (interpreted as the composition comprising a medium, claims 140 and 141) (paragraph [0074]). Berg teaches that liposomes for use in accordance with the present invention are liposomes which are stable in biological media and fluids such as blood, serum, feces, urine, etc. (interpreted as comprising medium, claims 140 and 141) (paragraph [0057]).
Berg meets all the limitations of the claims and, therefore, anticipates the claimed invention.
Response to Arguments
Applicant’s arguments filed December 16, 2025 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) Berg does not teach the use of two protecting vehicles and two protected nucleic acid sequences as required by the present quality control composition, nor does Berg describe that the protecting vehicles are bacteria, viruses or eukaryotic cells; Berg teaches one protected nucleic acid sequence as an internal control (Applicant Remarks, pg. 25, first full paragraph through third full paragraph).
Regarding (a), please see the discussion supra regarding what is recited in claims 109 and 123. Moreover, as noted in MPEP 2112.01(I),
where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). "When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).
Applicant’s assertion that Berg does not teach the use of two protecting vehicles and two protected nucleic acid sequences as required by the present quality control composition, nor does Berg describe that the protecting vehicles are bacteria, viruses or eukaryotic cells; Berg teaches one protected nucleic acid sequence as an internal control, is not found persuasive. The Examiner disagrees.
Berg teaches:
The use of internal control (IC) nucleic acids contained or encapsulated within non-viable particles, where such non-viable particles are in the form of liposomes, protein coats or non-viable genetically modified organisms, which can be designed based on the particular target nucleic acid that is to be analyzed (interpreted as nucleic acids within at least two non-viable particles/protecting vehicles) (paragraphs [0011], lines 1-17; and [0032], lines 1-6).
The production of the internal control (IC) and entrapment of it into liposomes was described in Example 1, where liposomes with entrapped IC were isolated (interpreted as nucleic acids within at least two non-viable particles/protecting vehicles) (paragraphs [0103] and [0107]).
DNA was isolated from an in vivo sample containing C. Trachomatis spiked with entrapped IC, wherein a cell suspension of a cultured C. trachomatis L2 strain was spiked with liposomes/IC DNA complex was prepared as described above; and Chlamydia and IC DNA was prepared from the cells/liposomes, wherein the purified Chlamydia and IC DNA was analyzed in a multiplex PCR using primer sets (interpreting the entrapped IC and bacterial cell suspensions as two or more protecting vehicles comprising protected nucleic acid sequences).
The samples can be derived from in vitro sources including cultured cells, bacteria or viral particles; or in vivo sources such as human, plant or animal sources such as patients including viruses (interpreted as comprising nucleic acids that encode a virus gene).
The use of nucleic acid-based analysis in the field of diagnostic testing including for the diagnosis of microbiological pathogens and genetic disorders, the discovery of unknown infectious agents and improved diagnostic tools, wherein nucleic acid-based analysis can be either qualitative or quantitative and can involve nucleic acid-based amplification techniques (interpreted as nucleic acid testing, NAT).
Berg teaches all of the limitations of the claims including a plurality of protected nucleic acid sequences as recited in claim 109, and performing a NAT as recited in claim 123. Thus, the claims remain rejected.
Claim Rejections - 35 USC § 103
The rejection of claims 109-111, 116, 123 and 140 is maintained, and claim 141 is newly rejected, under 35 U.S.C. 103 as being unpatentable over Berg et. al. (hereinafter “Berg”) (US Patent Application Publication 20110065092, published March 17, 2011) in view of Witt et. al. (hereinafter “Witt”) (Journal of Virological Methods, 1999, 79, 97-111).
The teachings of Berg as applied to claims 109-111, 116, 123, 140 and 141 are described supra.
Berg does not specifically exemplify a composition comprising a protecting vehicle comprising viable particles (claim 130, in part).
Regarding claims 130 (in part), Witt teaches that accurate HIV-1 RNA quantitation with nucleic acid amplification assays (NAAA) is partly dependent on overall assay design to ensure proper and reproducible functioning in the presence of endogenous interfering substances present in a clinical specimen, or exogenous interfering substances introduced as a result of specimen collection or handling, wherein the study tested various methods of evaluating interfering substances that could potentially affect the outcome of HIV-1 RNA amplification in a NAAA (interpreted as nucleic acids in NAT; and a first protected nucleic acid sequence comprising endogenous RNA, claims 109 and 123) (Abstract, lines 1-5). Witt teaches that clinical specimens from HIV-1 seronegative subjects containing various endogenous interferents were evaluated with and without an HIV-1 RNA spike to assess recovery and specificity, respectively, with a non-PCR NAAA (NASBA HIV-1 RNA QT) that incorporates Boom methodology for nucleic acid extraction, wherein additional specimens were prepared to simulate various circumstances that might occur during specimen preparation to result in the introduction of exogenous interferents, wherein potential interference include abnormally elevated levels of physiological biomolecules, cellular components of blood, anticoagulants, bacterial contaminants and anti-retroviral drug (interpreted as a quality control composition; nucleic acids in NAT; a first protected nucleic acid sequence comprising endogenous RNA; interpreting cells to be the protecting vehicles; a second protected nucleic acid sequence comprising exogenous RNA; capable of being recovered in an extraction step of the NAT; obtaining a sample; providing a quality control composition; performing a NAT on each in parallel or in sequence, claim 130) (Abstract, lines 5-11; and pg. 98, col 2, first partial paragraph). Witt teaches that the spiked HIV-1 RNA copies in the clinical specimens reported by the assay were 99% of the copies reported for a positive index control (normal plasma plus HIV-1 RNA spike), such that compared to the amplification levels of the three internal assay calibrators obtained for normal plasma controls, no differences in the amplification levels of the calibrators for each type of specimen were observed, wherein the result indicated that the interferents examined did not affect adversely assay function (interpreted as first protected nucleic acid sequences; carrying out a NAT; and comparing the results, claims 109 and 123) (Abstract, lines 12-17). Witt teaches that the addition of known PCR interferents (hemoglobin and heparin) and AZT to isolated HIV-1 RNA resulted in a substantial reduction of amplification and invalid results, whereas no inhibition was observed when these interferents were added to the test system prior to isolation; these results directly demonstrate the efficient removal of such interferents during the NASBA HIV-RNA QT isolation procedure, wherein several approaches to investigate interferences described in the study can be utilized for the evaluation of other assays using nucleic acid amplification technology (interpreted as using NAT; and comparing results, claims 109 and 123) (Abstract, lines 17-22). Witt teaches that specimens were obtained from HIV-1 seronegative subjects with defined medical conditions or elevated physiological analytes; hemolyzed specimens were prepared by incubating whole blood from volunteer donors for 7-10 days; specimens from pregnant women were obtained from healthy clinic patients and healthy volunteer donors; and specimens contaminated with bacteria were prepared by adding bacillus cereus, Staphylococcus epidermidis, and Pseudomonas fluorescens at a concentration of 1 x 107 CFU/ml separately to individual plasma specimens and incubating the specimens prior to HIV-1 RNA spike addition and NAAA testing, wherein all bacterial species were grown using standard suspension methods (interpreted as first protected nucleic acid sequences; carrying out a NAT; obtaining a test sample; providing a QC composition; performing the NAT; a protecting vehicles including bacteria or HIV-1 virus; integrated into the endogenous nucleic acid; comprising native sequences and non-native sequences; a viable pathogenic organism; incubated in a medium; and comprising additional protected nucleic acid sequences, claims 109, 110, 111, 116, 123, 130 and 140) (pg. 99, col 1; and col 2, first partial paragraph, lines 1-2). Witt teaches that the specimens contaminated with bacteria were each tested with and without HIV-1 RNA spike once at a final volume, wherein positive and negative index controls were included with each NAAA analysis (interpreting bacteria and HIV-1 RNA as multiple second protecting vehicles containing exogenous nucleic acid; and interpreting controls as multiple first protecting vehicle containing endogenous nucleic acids, claim 109 and 130) (pg. 100, col 1, last full paragraph).
It is prima facie obvious to combine prior art elements according to known methods to yield predictable results; the court held that, "…a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. KSR International Co. v. Teleflex Inc., 550 U.S. ___, ___, 82 USPQ2d 1385, 1395 (2007); Sakraida v. AG Pro, Inc., 425 U.S. 273, 282, 189 USPQ 449, 453 (1976); Anderson’s-Black Rock, Inc. v. Pavement Salvage Co., 396 U.S. 57, 62-63, 163 USPQ 673, 675 (1969); Great Atlantic & P. Tea Co. v. Supermarket Equipment Corp., 340 U.S. 147, 152, 87 USPQ 303, 306 (1950)”. Therefore, in view of the benefits of evaluating nucleic acid amplification technology performance with specimens containing interfering substances as exemplified by Witt, it would have been prima facia obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of using non-viable particles such a liposome particles and/or viral protein coat particles that can be used to encapsulate internal control nucleic acid sequences for use as a quality control in nucleic acid testing as disclosed by Berg to include the methods of assessing accurate nucleic acid quantification in NAA assays of clinical specimens comprising endogenous or exogenous interfering substances as taught by Witt, with a reasonable expectation of success in assessing the ability of NAA assays to function properly and reproducibly in the presence of interfering substances; in quantifying an amount of viral and/or bacterial nucleic acids in a biological sample by comparing the amplification levels of specimens with internal assay calibrators obtained for normal plasma controls; as well as, the amplification levels of internal control nucleic acids that are protected against degradation by a liposome and/or protein coat particle; and/or in assessing the ability of different sample isolation procedures to remove interfering contaminants in order to reduce false positives and false negative results that can lead to the erroneous interpretation of data and the inadequate or incorrect treatment of patients.
Thus, in view of the foregoing, the claimed invention, as a whole, would have been obvious to one of ordinary skill in the art at the time the invention was made. Therefore, the claims are properly rejected under 35 USC §103 as obvious over the art.
Response to Arguments
Applicant’s arguments filed December 16, 2025 have been fully considered but they are not persuasive. Applicants essentially assert that: (a) Berg does not teach the use of two protecting vehicles and two protected nucleic acid sequences tested in the NAT; and nothing in the combination of Berg and Witt would have motivated one of skill to arrive at the present quality control composition comprising TWO protecting vehicles for TWO protected nucleic acids that are tested in the NAT (Applicant Remarks, pg. 25, last partial paragraph through pg. 26, first full paragraph); and (b) a quality control composition as exemplified in Figure 3 has advantages over previously known quality controls. As shown in Figure 3, a second protecting vehicle is depicted as an E. coli that now expresses non-natively present genetic material, e.g ., a sequence from mecA; and the second protecting vehicle, E. coli has a different nucleic acid sequence composition, such that multi-organism controls as described herein can provide nucleic acid sequences in separate protecting vehicles, with advantages of ease of construction, multi-use potential, safety enhancements, etc. (Applicant Remarks, pg. 26, last partial paragraph through pg. 27, first partial paragraph).
Regarding (a), please see the discussion supra regarding the Examiner’s response to Applicant’s arguments with regard to two protecting vehicles; and the teachings of Berg. Applicant’s assertion that Berg does not teach the use of two protecting vehicles and two protected nucleic acid sequences tested in the NAT; and nothing in the combination of Berg and Witt would have motivated one of skill to arrive at the present quality control composition comprising TWO protecting vehicles for TWO protected nucleic acids that are tested in the NAT, is not found persuasive. As noted supra, the Examiner contends that Berg teaches a plurality of internal control (IC) nucleic acids within protecting vehicles; as well as, virus nucleic acids within protecting vehicles. The combined references of Berg and Witt teach all of the limitations of the claims including a plurality of protected nucleic acid sequences as recited in claim 109, and performing a NAT as recited in claim 123. Thus, the claims remain rejected.
Regarding (b), Applicant’s argument that the quality control composition of Figure 3 has advantages over previously known quality controls, where a second protecting vehicle is depicted as E. coli that now expresses non-natively present genetic material (e.g., a sequence from mecA) and the second protecting vehicle, E. coli, has a different nucleic acid sequence composition, such that multi-organism controls as described herein can provide nucleic acid sequences in separate protecting vehicles, with advantages of ease of construction, etc., is not found persuasive. Applicant is reminded that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. As an initial matter:
No evidence supporting the unexpected results has been provided by Applicant.
Applicant’s has not provided any evidence of improved properties that are reasonably commensurate in scope with the claimed invention.
There is no nexus or co-extensiveness between Applicant’s asserted improvements and the steps as recited in claims 109 and 123.
Instant claims 109 and 123 do not recite the compositions as shown in Figure 3 including: an MRSA sequence comprising a portion of the mecA sequence, an E. coli second protecting vehicle expressing a mecA sequence, multi-organism controls, mixing and matching, and/or screening for the presence of a mecA target sequence.
Applicant has not pointed to where these advantages or surprising results were recognized in the as-filed Specification.
Applicants have not clearly stated the nature of the unexpectedly improved properties that Applicant asserts are not taught in the prior art.
Evidence has not been provided that the "superior results" asserted by Applicant were unknown in the prior art.
Additionally, MPEP 2112.01(II) states that products of identical chemical composition cannot have mutually exclusive properties. Because Berg (and Berg and Witt) teach all of the limitations of claims 109 and 123, the product of Berg will inherently provide the same unexpected benefits as asserted by Applicant. Thus, the claims remain rejected.
New Objection/Rejections
Claim Objections
Claim 109 is objected to because of the following informalities: Claim 109, lines 13-14 and 21-23 recites two Markush groupings, but uses the term “or”, wherein the phrases: “selected from the group consisting of an antibiotic…and a virus gene” and “selected from the group consisting of a virus…and an inactivated, non-viable or non-pathogenic organism” is more appropriate.
Appropriate correction is required.
Conclusion
Claims 109-111, 116, 123, 140 and 141 are rejected.
THIS ACTION IS MADE FINAL. 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 AMY M BUNKER whose telephone number is (313) 446-4833. The examiner can normally be reached on Monday-Friday (6am-2:30pm).
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/AMY M BUNKER/Primary Examiner, Art Unit 1684