DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
2. Claims 1-15 are under consideration.
Priority
3. Receipt is acknowledged of certified copies of papers required by 35 CFR 1.55. Should Applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CRF 41.154(b) and 41.202(e). Therefore, the effective filing date for purposes of applying prior art is 22 July 2024.
Failure to provide a certified translation may result in no benefit being accorded for the non-English translation.
Information Disclosure Statement
4. The information disclosure statements (IDS) submitted on 12 November 2024 and 22 July 2024 were filed before the mailing date of the Non-Final Office Action. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
5. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
6. Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
7. Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
See Figures 1-3 and 11. Defining the sequences in another part of the specification is not sufficient.
Specification
8. The attempt to incorporate subject matter into this application by reference to the recited reference sequence IDs, such as GenBank accession numbers, NCBI references, and protein IDs is ineffective because they do not provide the actual sequences that they are referring to.
Claim Objections
9. Claims 1-3, 6-7, 9-11 and 13-14 are objected to because of the following informalities:
Regarding claim 1, there appears to be a word missing between “comprises two” and “with 90 to 130 base pairs”, in addition Examiner recommends rewriting “when the product is not present, the influenza A and B viruses” as “when one product is not present, the influenza A or B virus” for clarity.
Regarding claim 2, there should be a comma after “feces” for clarity.
Regarding claim 3, every instance of “to” before “SEQ ID NO:” should be rewritten as “of” or “comprising” for clarity.
Regarding claim 6, “the reverse primer” before “of the second primer pair” should be deleted.
Regarding claims 7, 11, 13, and 15, every instance of “providing a x probe, which is a nucleotide sequence,” should be rewritten as “providing a first probe which is a nucleotide sequence, wherein” for clarity.
Regarding claim 7, a comma should be added after “the first probe” in the last line.
Regarding claim 9, a comma should be added after “the second primer pair” in the last paragraph.
Regarding claim 10, there should be a comma after “the second primer pair”; additionally, “a sequence of ribonuclease P of the human to SEQ ID NO: 14” should be rewritten “a sequence of human ribonuclease P of SEQ ID NO: 14” for clarity.
Regarding claim 11, a comma should be added in the last line after “second probe” for clarity.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
10. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
11. Claims 1-15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 1, 7, 9, and 11-15, “its complementary nucleotide sequence” is unclear because a complementary sequence cannot be selected from the group consisting of the SEQ ID NO and a sequence 80% to about 99% identical to the SEQ ID NO. The complementary sequence will have a much lower percent identity than 80%.
Claims 2-11, which depend on claim 1, are similarly rejected.
Claim 8, which depends on claim 7, is similarly rejected.
Claims 10-11, which depend on claim 9, are similarly rejected.
Claims 13-15, which depend on claim 12, are similarly rejected.
The term “about” in claims 1, 7, 9, and 11-15 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The specification merely defines the term as “is intended to encompass numbers that are within a reasonable range” (¶ [0035]), but does not explicitly define the range. This range could be interpreted differently by different people.
Claims 2-11, which depend on claim 1, are similarly rejected.
Claim 8, which depends on claim 7, is similarly rejected.
Claims 10-11, which depend on claim 9, are similarly rejected.
Claims 13-15, which depend on claim 12, are similarly rejected.
Regarding claims 1 and 12, the iteration of “first primer pair” and “second primer pair” is unclear because “pair” implies two primers, but the claims require three. Examiner is interpreting this to mean that there is a mix of all three primers in each “pair”, wherein only one forward and one reverse primer are bound to each target of interest. Examiner suggests adding each pair option in a list fashion.
Claims 2-11, which depend on claim 1, are similarly rejected.
Claims 13-15, which depend on claim 12, are similarly rejected.
Regarding claims 4 and 5, the recitation of “the forward primer of the first primer pair” and “the reverse primer of the second primer pair” is unclear because there are multiple forward primers in the first primer pair and multiple reverse primers in the second primer pair. This could be interpreted as one forward/reverse primer has that ratio, or that the mixture of the multiple forward/reverse primers has that ratio. Therefore, there are multiple interpretations.
Claim 6, which is depends on claim 5, is similarly rejected.
See Ex parte Miyazaki, 89 USPQ2d 1207 (BPAI 2008) ("[R]ather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amenable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. §112, second paragraph, as indefinite.").
Claim Rejections - 35 USC § 112(a) – Written Description
12. The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
13. Claims 1-8 and 12-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The following quotation from MPEP § 2163 is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
“The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice .... reduction to drawings .... or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.”
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. Therefore, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
Claims 1-15 are rejected as lacking adequate descriptive support for a mutated primer or probe which results in a functional primer or probe. In support of the claimed genus (primers or probes with 80% or higher identity to the recited sequences), the application discloses figures 1-3, which shows the alignment of the primer and probe sequences to the genome in which they are derived, and table 1 which shows the primer and probe sequences. No derivatives or variants or mutants thereof are disclosed that can achieve this functionality. Thus, the application fails to provide examples of any species within the claimed genus.
Further, while the claims provide both a structure and a function, the application fails to draw any correlation between the two. i.e., there is no evidence that any mutation can still retain functionality and ability to bind to the template sequence. Moreover, no correlation has been made to which mutations can be made in order to achieve the claimed functionality. Lastly, the specification does not establish any additional mutated sequences. The teachings of the art also fail to indicate that, without such evidence, those in the art would have expected the full scope of the claimed primers and probes would confer the claimed functionality. For example, a search of the art indicates that mismatches at the 3’ end of primers are known to be exceptionally detrimental to PCR priming and pose a serious problem for nucleic acid amplification using PCR (Stadhouders, January 2010, J. Mol. Diagn. 12(1): 109-117) (Discussion, ¶ 1) and that single mismatches instigate a broad but consistent variety of effects depending on mismatch type, position, and the type of master mix used (Discussion, ¶ 1). In addition, Rodriguez (2015, PCR Primer Design Second Edition, Humana Press, Chapter 3) teaches that each primer needs to be validated using BLAST to confirm target specificity and that in silico tools could be used for predicting potential PCR products and searching of possible mispriming (Page 44, ¶ 3-4). These results contradict the claimed functional characteristic of every primer and probe with 80% or more identity to the claimed sequences.
Thus, in view of the above, there would have been significant uncertainty as to which mutated primers and probes would be able confer the claimed functionality. In view of this uncertainty and the lack of any examples of the claimed genus, the claims are rejected for lack of adequate written description support.
Claim Rejections - 35 USC § 112(a) – Enablement
14. In making a determination as to whether an application has met the requirements forenablement under 35 U.S.C. 112 ¶ 1, the courts have put forth a series of factors. See, In reWands, 8 USPQ2d 1400, at 1404 (CAFC 1988). The factors considered include: (1) the breadth of the claims, (2) the nature of the invention, (3) the relative skill of those in the art, (4) the presence or absence of working examples, (5) the amount of direction or guidance provided, (6) the state of the prior art, (7) the level of predictability in the art, and (8) the quantity of experimentation necessary.
15. Claims 1-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for primers and probes with the full sequences as recited, does not reasonably provide enablement for any mutated primers or probes. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The claims recite a method or kit for detecting influenza A and B viruses, using primers or probes or derivatives thereof.
The nature of the invention are products and methods for using the primers or probes or derivatives thereof.
The level of skill of one of ordinary skill in this art is high.
The specification discloses figures 1-3, which shows the alignment of the primer and probe sequences to the genome in which they are derived, and table 1 which shows the primer and probe sequences. The specification does not show any other mutations/modifications that will work.
A search of the art indicates that mismatches at the 3’ end of primers are known to be exceptionally detrimental to PCR priming and pose a serious problem for nucleic acid amplification using PCR (Stadhouders, January 2010, J. Mol. Diagn. 12(1): 109-117) (Discussion, ¶ 1) and that single mismatches instigate a broad but consistent variety of effects depending on mismatch type, position, and the type of master mix used (Discussion, ¶ 1). In addition, Rodriguez (2015, PCR Primer Design Second Edition, Humana Press, Chapter 3) teaches that each primer needs to be validated using BLAST to confirm target specificity and that in silico tools could be used for predicting potential PCR products and searching of possible mispriming (Page 44, ¶ 3-4). These results contradict the claimed functional characteristic of every primer and probe with 80% or more identity to the claimed sequences.
Since the art teaches that it is unpredictable if primer and probe mutations will be functional in PCR and the specification does nothing to ameliorate these concerns, one would be burdened with undue experimentation to use the methods of the instant claims are broadly as they are currently claimed.
Claim Rejections - 35 USC § 103
16. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
17. The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
18. Claims 1-8 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Poetter (WO 2013049891 A1; published 11 April 2013) in view of NCBI reference sequence NC_007367.1 (13 August 2018); GenBank OP775695.1 (31 December 2022); GenBank CY115392.1 (11 April 2012); GenBank MT343766.1 (21 April 2020); Rychlik (1989, Nucleic Acids Research, 17(21): 8543-8551); Buck (1999, Biotechniques, 27: 528-536); Irshad (28 May 2016, World J. Gastroenterol., 22(20): 4824-4834); and King (2003, Journal of Virological Methods, 107: 53-61).
Regarding claims 1, 3, and 7-8, Poetter teaches “a method of screening a sample for a multiplicity of respiratory pathogens” using PCR by subjecting the nucleic acid to amplification, wherein an aqueous primer pair directs the amplification of a region of nucleic acid from a respiratory pathogen, the number of primer pairs being selected on the basis of the number of pathogens desired to be screened… wherein the amplicon is captured by hybridizing to an oligonucleotide probe that is complementary to a region of the amplicon… (¶ [0009]). Poetter also includes a list of all the respiratory pathogens that can be detected, including Influenza A and Influenza B (¶ [0014]), as well as the specific nucleic acid targets (¶ [0015]). Poetter also teaches that the primer pairs and probes are selected from the SEQ ID NOs listed in Table 8 and that two or more primer pairs + probes are selected, up to 18 (¶ [0134J). RT-PCR was used (¶ [0030] and [0033]). In summary, Poetter teaches a method of detecting and identifying different respiratory pathogens by using a mix of primers and probes specific for each pathogen to be detected in RT-PCR. Poetter does not teach the specific SEQ ID NOs.
Regarding the specific sequences for the primers and probes being used, the following sequences were found on NCBI BLAST:
NCBI Reference Sequence NC_007367.1, which contains SEQ ID NOs: 1, 3, and 9. Note that SEQ ID NO: 9 is found between the two primers:
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The product of SEQ ID NOs: 1 and 3 as the forward and reverse primers, respectively, results in a product that is 119 bases length. This product reads on SEQ ID NO: 12:
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GenBank OP775695.1, which contains SEQ ID NOs: 2-3 and 9. Note that SEQ ID NO: 9 is found between the two primers:
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The product of SEQ ID NOs: 2 and 3 as the forward and reverse primers, respectively, results in a product that is 119 bases in length.
GenBank CY115392.1, which contains SEQ ID NOs: 4-5 and 10. Note that SEQ ID NO: 10 is found between the two primers:
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The product of SEQ ID NOs: 4 and 5 as the forward and reverse primers, respectively, results in a product that is 107 bases in length. This product reads on SEQ ID NO: 13:
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GenBank MT343766.1, which contains SEQ ID NOs: 4, 6, and 10. Note that SEQ ID NO: 10 is found between the two primers:
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The product of SEQ IS NOs: 4 and 6 as the forward and reverse primers, respectively, results in a product that is 107 bases in length.
Rychlik teaches it is routine and predictable to make primers for DNA amplification wherein primers are designed to a known oligonucleotide sequence. Rychlik teaches criteria to design/choose suitable primers for DNA amplification (see whole document and Abstract). Buck expressly provides evidence of the equivalence of primers. Specifically, Buck invited primer submissions from a number of labs (39) (Page 532, Column 3), with 69 different primers being submitted (Page 530, Column 1). Buck also tested 95 primers spaced at 3 nucleotide intervals along the entire sequence at issue, thereby testing more than 1/3 of all possible 18 met primers on the 300 base pair sequence (Page 530, Column 1). When Buck tested each of the primers selected by the methods of the different labs, Buck found that every single primer worked (Page 533, Column 1). Further, every single control primer functioned as well (Page 533, Column 1). Buck expressly states "The results of the empirical sequencing analysis were surprising in that nearly all of the primers yielded data of extremely high quality (Page 535, Column 2)." Therefore, Buck provides direct evidence that all primers would be expected to function, and in particular, all primers selected according to the ordinary criteria (See Table 1 below).
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This clearly shows that every primer would have a reasonable expectation of success. Therefore, it would have been obvious to one of ordinary skill at the time of filing to take the method of Poetter and further replace their primers and probes with the ones as claimed. Since all the sequences of the claimed primers and probes are present and meet primer criteria, they are obvious primers that will function in the assay of Poetter to yield predictable results.
Adding multiple primers for each influenza virus aids in covering variance between different strains, which would allow for a more accurate result. Irshad teaches multiplex qPCR assays, which allow for “simultaneous detection of multiple pathogens in a single assay. Recently, several PCR based assays coupled with oligonucleotide microarray technology have been designed to allow for the simultaneous detection and genotyping of several viruses, including blood borne pathogens, respiratory viruses, and adenoviruses.” (Introduction, ¶ 4). Therefore, it would have been further obvious to add multiple primer pairs in the same reaction. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support 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. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
If either influenza A or B is present, their PCR products will be the respective sizes from the primer pairs as discussed supra, which are all between 90 and 130 base pairs. If the template sequences are not in the sample, their respective products noted above will not be amplified in the RT-PCR reaction.
Regarding the distance between the primers and probes, King teaches Figure 1, which illustrates that probes should fall between the forward and reverse primers in a TaqMan assay:
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Therefore, it would have been obvious to one of ordinary skill before the filing date to use a sequence between the forward and reverse primers as the probe. The combination of familiar elements is likely to be obvious when it does no more than yield predictable results. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, A.). A rationale to support 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. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
Taken together, it would have been obvious to use the method of Poetter to detect influenza A and B viruses using the primers and probes made obvious above, in a single RT-PCR reaction.
Regarding claim 2, Poetter further teaches that the sample can be blood, saliva, mucus, feces, or urine (¶ [0046]).
Regarding claims 4-6, Poetter further teaches Figure 3 and 4, which show that the primer concentrations varied between different primer pairs, but primer pairs had the same concentration for both the forward and reverse primers. This would result in a ratio of 1:1. Poetter also discusses that primer concentrations were optimized (¶ [0147J). Therefore, it would have also been obvious that primer concentrations and ratios are result-effective parameters that one of ordinary skill would routinely optimize. It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since Applicant has not disclosed that the specific limitations recited in instant claims are for any particular purpose or solve any stated problem, and the prior art teaches that parameter magnitudes that are encompassed by instant claims, often vary according to the sample being analyzed and various matrices, solutions and parameters appear to work equally as well, absent unexpected results, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the art.
Regarding claims 12-13, Poetter further teaches “Table 8 provides a list of primers and capture probes used in the assay method and kit for respiratory pathogens. At least two primer pairs and corresponding probes are used in the kit. By "at least two" means 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1, 12, 13, 14, 15, 16, 17 or 18.” (¶ [0182]). Therefore, it would be obvious to one of ordinary skill before the effective filing date to take any of the primer and probes made obvious supra and further add them to a kit.
19. Claims 9-11 and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Poetter (Supra), NC_007367.1 (Supra), GenBank OP775695.1 (Supra), GenBank CY115392.1 (Supra), GenBank MT343766.1 (Supra), Rychlik (Supra), Buck (Supra), Irshad (Supra), and King (Supra) as applied to claims 1, 3, and 7-8 above, and further in view of Emery (February 2004, CDC Emerging Infectious Diseases, 10(2)) and GenBank AK312900.1 (24 May 2008).
Regarding claims 9-11, Poetter, NC_007367.1, GenBank OP775695.1, GenBank CY115392.1, GenBank MT343766.1, Rychlik, Buck, Irshad, and King make claim 1 obvious, as discussed supra. All discussions thereon incorporated here.
Poetter further teaches that a control sequence can be derived from the human MYL3 gene (¶ [0111]). Poetter does not teach that the control can be human ribonuclease P. However, Emery teaches RT-PCR in the context of SARS-CoV detection (Abstract), wherein “False-negative results due to poor quality nucleic acid or presence of RT-PCR inhibitors can also be a concern. We addressed this by simultaneously testing for the human RNase P gene, which should be present in all adequately collected samples.” (Discussion, ¶ 2). Human RNase P will be present in all samples that contain human cells
Therefore, it would have been obvious to one of ordinary skill to take the method made obvious by Poetter and further replace their control with human RNase P primers and probes to ensure samples were properly collected. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
Further, GenBank AK312900.1 contains SEQ ID NOs: 7-8 and 11. Note that SEQ ID NO: 11 is found between the two primers, which is obvious as discussed by King supra:
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The product of SEQ ID NOs: 7 and 8 as the forward and reverse primers, respectively, results in a product that is 71 bases in length. This product reads on SEQ ID NO: 14:
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The obviousness of primer and probes are discussed by Rychlik and Buck supra.
Regarding claims 14-15, Poetter further teaches “Table 8 provides a list of primers and capture probes used in the assay method and kit for respiratory pathogens. At least two primer pairs and corresponding probes are used in the kit. By "at least two" means 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1, 12, 13, 14, 15, 16, 17 or 18.” (¶ [0182]). Therefore, it would be obvious to one of ordinary skill before the effective filing date to take any of the primer and probes made obvious supra and further add them to a kit.
Other Prior Art
20. Examiner notes Norgen (2021, COVID-19/Influenza (A&B) TaqMan RT-PCR Kit) as unused prior art. Norgen teaches a RT-PCR kit for detecting SARS-CoV-2, influenza A, and influenza B and “The assay can be used on RNA isolated from nasopharyngeal swabs, oropharyngeal swabs and saliva samples collected from individuals with clinical signs/symptoms related to SARS-CoV-2 and Influenza A and B infection.” (Intended Use). Norgen further teaches “human RNase P transcript as an internal control target to monitor for PCR inhibition, and to validate the quality of the sample and the detection result” (Product Description). This, in combination with the obvious primer and probe sequences would make claims 1-15 obvious.
Conclusion
21. No claim is allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KRISTINA E LY whose telephone number is (571)272-5169. The examiner can normally be reached Monday - Thursday, 8:00 am - 5:00 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KRISTINA E. LY/Examiner, Art Unit 1671 /Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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