DETAILED ACTION
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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-11 and 15) in the reply filed on 12/6/2025 is acknowledged.
Claims 12-14 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/24/2022, 4/2/2024, 5/17/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner, except where noted.
The information disclosure statement filed 4/2/2024 fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language. Specifically, citation no. 2 does not have an English translation or explanation of relevance provided, and so this reference has not been considered.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above. Specifically, the paragraph is missing in the instant specification.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, 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.
Specification
The disclosure is objected to because of the following informalities: the Sequence Incorporation by Reference paragraph is missing, as noted above.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-11 and 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.
Claim 1 is rejected because the scope of the claim is indefinite relative to the hybridization of the set of primers and the target nucleic acid. In the instant specification, para. 20 defines a target nucleic acid as “a nucleotide sequence to be detected and/or amplified or a nucleic acid comprising a nucleotide sequence complementary to the nucleotide sequence to be detected and/or amplified.” The paragraph goes on to state that a target can be double stranded with its complement strand, and one or both of the double strands can be referred to as the “target nucleic acid.” Thus, the target may exist as a double stranded nucleic acid, but this is not required.
In the instant claim, the first primer hybridizes, at its 3’ end, to a “complementary strand of partial polynucleotide A’ at the 5’ terminus of a target nucleic acid.” If the target is only single stranded, it is unclear how the first polynucleotide would function as a primer, as hybridizing to the 5’ end of the target nucleic acid would not result in extension during amplification. If the target is double stranded, then the first primer may hybridize to the second strand that is complementary to partial polynucleotide A’, which would be a 3’ end that would thus allow for extension.
The second primer is described as binding to “partial polynucleotide B’ at the 3’ terminus of the target nucleic acid” at the 3’ end of the primer. It is unclear if “partial polynucleotide B’” is on the same strand as “partial polynucleotide A’” or is on a different strand. If they are on different strands, then the primers would potentially be acting upon the same strand (as the first primer is potentially hybridizing to the complement of partial polynucleotide A’), and in this scenario, one strand of the double stranded target would not be amplified.
Thus, the scope of the claim is indefinite relative to the full scope of the definition of “target nucleic acid” in the instant specification, and thus renders the structure and function of the primers unclear. It will be interpreted as though the primers are acting as shown in Figures 1-1 and 1-2, and Applicant is encouraged to amend the claim to more clearly recite the structure of the target, potentially by clearly noting first and second strands of the target, and how the primers bind relative to said target strands.
Claims 2-11 and 15 are rejected based on their dependence on rejected claim 1.
Claim 2 is rejected because in line 3, it recites “a complementary strand of the partial polynucleotide A’ of the target nucleic acid.” Polynucleotide C is recited in claim 1 as being capable of binding competitively with polynucleotide A of the first primer, and polynucleotide A is stated to hybridize to a “complementary strand of partial polynucleotide A’.” By then stating “a complementary strand” again in claim 2, this renders it unclear as to whether the same portion of partial polynucleotide A’ is recited in claims 1 and 2. If two different portions are recited, then it is further unclear how the competitive function of polynucleotide C would be possible in all embodiments of the claims, as polynucleotide A and C could then bind to completely different portions of partial polynucleotide A’. This renders the claim indefinite.
Claim 15 is also rejected because it recites “two or more sets of primers according to Claim 1,” followed by “the nucleic acid amplification reaction using the two or more sets of primers.” In claim 1, a single set of primers is stated in the preamble to be associated with a nucleic acid amplification reaction. Thus, no nucleic acid amplification reaction is recited that uses two or more sets of primers, and so the recitation of “the nucleic acid amplification reaction using the two or more sets of primers” lacks sufficient antecedent basis. It is recommended to recite that each set of primers of the two or more sets of primers of the claim is designed for a different target nucleic acid.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-9 and 15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claims recite natural products.
Claim 1 is drawn towards a set of primers for target nucleic acid amplification. The second and third primers are particular nucleic acid sequences. The first primer must contain a tag that is independent of an amplification reaction. According to para. 31 of the instant specification, a sequence that is “independent of an amplification reaction” is not used as a template in said reaction, though how this may be accomplished is not specifically defined by the instant specification. Thus, the tag may be a sequence that has a particular secondary structure (e.g. a stem-loop) or a sequence that has an affinity for binding to a protein that blocks amplification. In both of these instances, the first polynucleotide would still remain a nucleic acid with a particular sequence, where said sequence could exist in nature. Thus, though it is not clear that oligonucleotides having the features recited in claim 1 exist in nature, the claimed oligonucleotides are, nevertheless, judicial exceptions because they are derived from naturally occurring molecules and are not required to possess any structural or functional differences relative to their naturally occurring counterparts. For example, the oligonucleotides of claim 1 are not required to include a fluorescently detectable label. As well, the oligonucleotides do not have a function that differs from that of the naturally occurring counterparts since, like the naturally occurring counterparts, the claimed oligonucleotides hybridize to specific nucleic acid sequences. MPEP 2106.04(c) II specifically notes that primers are considered products of nature that lack markedly different characteristics because they share the same sequence as their naturally occurring counterparts, and the ability of the primers to act as starting material is innate to DNA itself, and is not created or altered by the creation of the primers. As the primers of instant claim 1 currently each encompass natural products, the claim as a whole is directed to a group of products that are not markedly different from their naturally occurring counterparts.
Claim 2 depends on claim 1 and provides additional sequence limitations for the third primer. These additional limitations (being a certain percentage in common with a target sequence) still encompass natural products, and so the claim is directed to a judicial exception without significantly more for the same reasons described above for claim 1.
Claims 3-4 depend on claim 1 and specify proportion amounts of each of the primers to be included in the set of primers. These claims do not alter the structure or functions of the primers, and so the claims are directed to a judicial exception without significantly more for the same reasons described above for claim 1.
Claim 5 depends on claim 1 and recites the use of a label substance linked to the second polynucleotide. A “label substance” is not defined by the instant specification. Para. 63 notes that, “A label substance is not particularly limited, provided that it does not inhibit a nucleic acid amplification reaction.” Para. 24 notes that tags can be used for labeling, and para. 68 specifically states that a second polynucleotide tag (on the second polynucleotide) can be a tag for labeling. Thus, the use of an additional tag sequence can be considered to be encompassed by a “label substance,” where such a tag label has no restrictions on the type of sequence that it may be. Thus, this tag may simply be an extension of the sequence of the second primer, with no structural or functional components that would render it markedly different from a natural product. Thus, this claim is directed to a judicial exception without significantly more for the same reasons described above for claim 1.
Claim 6 depends on claim 1, adds a second tag with the same functional requirements as the first tag of claim 1 (in that it is independent of nucleic acid amplification reactions), and adds a fourth primer. No additional structures or functions of the primers are recited that differ from those of claim 1. Thus, this claim is directed to a judicial exception without significantly more for the same reasons described above for claim 1.
Claim 7 depends on claim 6 and provides additional sequence limitations for the fourth primer. These additional limitations (being a certain percentage in common with a target sequence) still encompass natural products, and so the claim is directed to a judicial exception without significantly more for the same reasons described above for claims 1 and 6.
Claims 8-9 depend on claim 6 and specify proportion amounts of each of the primers to be included in the set of primers. These claims do not alter the structure or functions of the primers, and so the claims are directed to a judicial exception without significantly more for the same reasons described above for claims 1 and 6.
Claim 15 recites a multiplex set of primers as claimed in claim 1, where the primers are specific to distinct target sequences. This claim does not add to or alter the structures or functions of the set of primers of claim 1, and so the claim is directed to a judicial exception without significantly more for the same reasons described above for claim 1.
Claim Interpretation
As the pending claims 1-11 and 15 are directed to or contain a “set of primers,” it is noted that the instant specification provides no specific definition for this term, and so this term confers no particular structure onto the primers of the set, nor a particular means of keeping the primers of a set together (e.g. packaged together in a kit or reagent mixture).
With regard to the final wherein clause of claim 1, where polynucleotide C must be capable of hybridizing competitively with polynucleotide A, the instant specification states that “when one of polynucleotide A of the first primer and polynucleotide C of the third primer hybridizes to the complementary strand of the target nucleic acid, the other cannot hybridize…” (para. 75). This paragraph goes on to state that this may occur when the third polynucleotide can bind to 50% or more nucleotides of the same target as polynucleotide A. Thus, though polynucleotide A and polynucleotide C may be identical, this is not required, and any polynucleotide meeting this 50% or more requirement will be considered to meet the competitive requirements of the instant claim.
This same competitive interpretation will be applied to claim 6, which requires that polynucleotides D and B be competitive, and a similar explanation is provided for these polynucleotides in para. 93 of the instant specification.
In claim 5, a “label substance” is not defined by the instant specification. Para. 63 notes that, “A label substance is not particularly limited, provided that it does not inhibit a nucleic acid amplification reaction.” Para. 24 notes that tags can be used for labeling, and para. 68 specifically states that a second polynucleotide tag (on the second polynucleotide) can be a tag for labeling. Thus, any substance that can be linked to the second polynucleotide will be considered to be encompassed by a “label substance,” including the use of an additional polynucleotide tag.
Further regarding a “label substance,” in claim 11, which recites that a label substance must be capable of binding to a polynucleotide tag, para.116 states, “The step of labeling is performed when the second primer of the set of primers contains the second polynucleotide tag or when the second primer of the set of primers contains a label substance capable of binding to another substance detectable via a secondary reaction. In such a case, the second polynucleotide tag or the label substance is added in the nucleic acid for detection containing the target nucleic acid. In the step of labeling, the reaction product is brought into contact with a label substance or a detectable substance, and thereby binding the label substance or the detectable substance to the second polynucleotide tag in the nucleic acid for detection containing the target nucleic acid.” This does not necessarily further limit the structure of the “label substance” in the claim. Thus, the “label substance” here will be interpreted as any substance capable of binding to the second tag and a solid-phase support, where the label substance can be used for detection.
Similarly, a “capture substance” as recited in claims 10-11 is stated in the instant specification to be “not particularly limited, provided that it can bind to the first polynucleotide tag. A preferable capture substance is a polynucleotide capable of hybridizing to the first polynucleotide tag,” (para. 112). Thus, in the context of the claims, any substance that can bind to the first polynucleotide tag while also being bound to a solid-phase support will be considered to be encompassed by a capture substance. It is noted that some embodiments of capture substance under this interpretation may overlap with those described for the label substance above.
Furthermore, the claims currently being examined are product claims, and have no requirement that the primers in the primer set be used simultaneously. Additionally, though components (such as the first polynucleotide tag) are specified to be “independent of the nucleic acid amplification reaction,” the actual performance of an amplification reaction is not required by the claims.
Regarding claim 15, this claim recites “a multiplex set of primers comprising two or more sets of primers.” This is still a product claim, and so actual use of the multiplex set of primers is not required. Additionally, “multiplex” is typically used in the art, in the context of primers and amplification reactions, to refer to a use of the primers, where they are capable of use simultaneously in a single reaction to act on different sequences. A multiplexing amplification reaction does not necessarily dictate primer structure or function, provided the primer sequences do not overlap in their target sequences. However, “multiplex” generally also means many or multiple (see Merriam Webster definition attached). MPEP 2111 states that claims must be given their broadest reasonable interpretation in light of the specification. Para. 106 of the instant specification states, “When two or more different target nucleic acids are to be detected, the nucleic acid amplification reaction can be performed on the test material obtained from the analyte sample using a multiplex set of primers that is a combination of two or more sets of the primers mentioned above designed to amplify two or more target nucleic acids.” Taken together, in light of the interpretations already provided above for the claims, a “multiplex set of primers” will be interpreted as primers simply designed to amplify multiple different target sequences, and thus, the sequences of the analogous primers within each set must be different, at least with regard to the portions of the primers that anneal to the targets
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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.
Claims 1-11 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Mitsuo et al. (WO 2018/038232) in view of Ezaki et al. (US 2010/0075305 A1).
It is first noted that all of the references to teachings in the Mitsuo reference are referring to the provided English Translation.
Mitsuo teaches methods related to amplification (Abstract). Specifically, the reference mentions both PCR and LAMP amplification methods, which respectively require thermocycling and isothermal conditions (paras. 2 and 5). In the method described in para. 10, the reference describes tags placed on primers that are independent of the amplification reaction and are placed at the 5’ end of each primer (see step (5)). The tags utilize spacers that are capable of stopping nucleic acid synthesis via a polymerase, and thus do not participate in the actual amplification of a target sequence (see steps (6)-(7)). This method as a whole results in amplification that can occur without thermocycling, and can be performed under isothermal conditions (para. 22). Mitsuo teaches that the first and second primers (that contain the first and second tags) can be based on conventional PCR primers (para. 23). The tags that are independent of the amplification reaction are specifically noted to not be used as a template during said amplification (para. 26). These independent tags can be used for detection and labeling (paras. 28-29).
However, though Mitsuo does teach the use of additional primers such as a third and fourth primer that do not contain tag sequences (see Figure 1 and para. 48 for example), these additional primers are not competitive with the first and second primers as claimed. It is noted that fifth and sixth primers are used in some of their examples, but these also do not contain tag sequences or appear to act competitively (see paras. 102-103).
Ezaki teaches methods for detecting target nucleic acids (Abstract). These methods can involve multiplex PCR with a plurality of primer sets (para. 6). Generally, Ezaki notes that primers can have tags that do not anneal to a target nucleic acid sequence (paras. 33 and 130). Ezaki notes that the primers may have a linker sequence between the tag and the annealing sequence (para. 131), but the reference does not specifically note that the linker may stop amplification, and so the tags are likely not independent of the amplification reaction as in Mitsuo. The tags of the invention are intended to be on the 5’ end of the primer sequences, with the target annealing sequence on the 3’ ends of the primers (para. 126). These 3’ ends would then attach to the target nucleic acids in a 5’ to 3’ direction (see Figure 14). In Example 8 of the reference, a set of tagged forward and tagged reverse primers is used (para. 226). As a means of comparison, untagged primers were also used, where the untagged forward and reverse primers were the same in sequence as the tagged forward and tagged reverse primers, but without the use of the tag sequences (para. 227). This comparative method was used to confirm that the tag methods of their invention produced successful amplification and were superior to the untagged primers (para. 231 and Figure 16).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the comparative reasoning of Ezaki with the invention of Mitsuo to arrive at the set of primers of instant claims 1 and 6. Mitsuo teaches that their isothermal amplification methods are an improvement to the versatility and primer design constraints required by LAMP (paras. 7-9). However, as a check to the method/primers of Mitsuo, the ordinary artisan would recognize that it would be beneficial to also attempt amplification using the same primers of the Mitsuo, but without the tag sequences. This would allow for the benefits of the tags to become clear, or, in the case where tagged primer design is ineffective, to recognize this issue before the primers are used for practical application. In Ezaki, tagged primers were shown to produce much more amplification product compared to non-tagged primers (see Figure 16), and so the benefits of the tags here are clear. As Mitsuo also teaches that their general amplification method is based on a novel principle (Abstract and para. 8), the ordinary artisan would be motivated to check the efficacy of the reaction with known and thoroughly tested amplification methods, and if the results of Mitsuo produce less product or are prone to more errors than typical LAMP or other isothermal amplification methods, the adoption of these methods may not be suitable for particular applications. There would be a reasonable expectation of success in developing these comparative primers as they would be based on the known annealing sequence of the tagged primers, and methods of primer design and amplification are generally well-known in the art (see paras. 77 and 103 of Ezaki in particular, which teach the use of primer design software that would be accessible to the ordinary artisan).
This would thus result in the use of the primers of Mitsuo, where two tagged primers are present and the tags act independently of the amplification reaction (which are analogous to the first and second primers of instant claims 1 and 6), and two untagged primers that act as comparisons (which are analogous to the third and fourth primers of instant claims 1 and 6). As these third and fourth primers would have the same annealing sequences as the first and second primers, and Mitsuo teaches that their primers are fully hybridized to the target sequence (see para. 10, step (2) and at least Figure 1), these primers would also meet the limitations of instant claims 2 and 7. As noted above in the “Claim Interpretation” section, the primers of the instantly claimed set have no requirements to be used together, and so the primers generated by the combination of Mitsuo in view of Ezaki is considered to be analogous to the claimed set of primers.
Thus, claims 1-2 and 6-7 are prima facie obvious over Mitsuo in view of Ezaki.
Regarding claim 3, Ezaki states that their tagged forward and reverse primers are provided at 0.1µM each, and the untagged forward and reverse primers are also provided at 0.1µM each (see paras. 226-227). According to the tables of paras. 228-229, 2µL volume was used for each primer mixture, with a total reaction volume of 20µL for both reactions, and so each primer should have similar molarity. In claims 3-4, the percentages used are taken from the total amount of the third primer used to the total amount of the first and third primer used. The claims do not specify that the primers must be together in solution. Similar wording is provided for claims 8-9, where the amount of second primer provided is compared to the total amount of the second and fourth primers, without a requirement that they be together in solution. Thus, in Ezaki, the amount of an untagged forward primer provided relative to the tagged forward and untagged forward primers is 50 mol%, and the amount of an untagged reverse primer relative to the tagged and untagged reverse primers is 50 mol%. In the rejection of claims 1-2 and 6-7 described above, the comparative primer methods of Ezaki are employed to test the tagged primers of Mitsuo. As the teachings of Ezaki are used for comparison, and the reference shows successful data analysis resulting from their comparisons (e.g. Figure 16), it would be prima facie obvious to provide the first, second, third, and fourth primers described above in the combination of Mitsuo in view of Ezaki in the concentrations suggested by Ezaki (i.e. to have all the primers provided at the same concentration). This would ensure that the comparative methods are accurately reflecting the different amplification abilities of the primers given their tagged or untagged status, without additionally accounting for the confounding factor of primers being provided at different concentrations. Limiting such confounding is typical for comparative experiments, and so this design would be within the skill and knowledge of the ordinary artisan. There would be a reasonable expectation of success as manipulating reagent concentrations is well-known in the art, as evidenced by Ezaki (e.g. paras. 36, 141-142, and 153).
Thus, claims 3-4 and 8-9 are prima facie obvious over Mitsuo in view of Ezaki.
Regarding claim 5, Mitsuo teaches that at least one of the first and second primers can contain a marking element that is a labeling substance (para. 10, steps (8)-(9)). Para. 26 notes that the first and second primers can have, in addition to the tags that are independent of the amplification reaction, tags that may be involved in the amplification reaction. Para. 29 notes that either of these tags can be a labeling tag that is used to detect amplification products. These labeling tags can contain fluorescent or chromogenic substances (para. 74).
Thus, claim 5 is prima facie obvious over Mitsuo in view of Ezaki.
Regarding claims 10-11, the “detecting device” is not defined by the instant specification, and so is not required to be a part of any particular reaction type (e.g. amplification, sequencing), and must simply have the structural and functional features listed in the claims.
Mitsuo teaches that targets may be detected utilizing solid-phase support array based methods with immobilized probes or beads with immobilized probes (paras. 93-94). The probes are designed based on specificity for hybridizing to an amplification product (para. 95). Detection can generally occur due to labeling elements placed on the first and second primers (para. 97), and paras. 26 and 28 state that the tags added to the primers that are independent of the amplification reaction can be designed to be hybridized to a detection probe. Para. 29 also notes that labeling tags that are independent of the amplification reaction are capable of hybridizing with labeling probes. Para. 91 also notes that target nucleic acids can be detected via hybridization of tags independent of the amplification reaction with probes. Mitsuo also teaches kits, where said kits can contain the primers of their invention, probes, and carriers that contain said immobilized probes (paras. 98-99).
Prior to the effective filing date of the claimed invention, it would have been prima facie obvious for one of ordinary skill in the art to use the teachings of Mitsuo to arrive at the kits of claims 10-11 with the combination of Mitsuo in view of Ezaki. Mitsuo teaches that the tags on their primers that are independent of an amplification reaction may be used for detection and labeling, and both may be attached to probes. Probes may also be immobilized on a solid support. The ordinary artisan would be motivated to combine these aspects so that detecting of targets can occur on a solid support. Specifically, this would involve creating probes on the solid support capable of hybridizing to the detection/labeling tags on the first or second primer. Including both types of probes would ensure that both strands of a potential amplification product could be immobilized and detected. By using probes on a solid support, this would allow for easy downstream capture and manipulation of particular strands and easier washing steps to remove excess reagents. As Mitsuo already teaches that primers, probes, and elements for holding probes can be placed in kits, and teaches all of the structures and functions of the primers and the probes presented in this paragraph and the paragraph above, there would be a reasonable expectation of success.
Thus, claims 10-11 are prima facie obvious over Mitsuo in view of Ezaki.
Regarding claim 15, Example 8 of Ezaki specifically notes that the method is multiplex amplification, where the tagged forward and reverse primers are all different sequences (the pairs are SEQ ID NOs: 1-18 for the forward primers and SEQ ID NOs: 19-36 for the reverse primers, which are different sequences, as noted in the Sequence Listing for the reference). Though these pairs are all designed to target portions of the Legionella pneumophila GTC 1279 DNA (para. 226), the exact nucleic acid sequences on the Legionella pneumophila GTC 1279 DNA amplified by each primer pair are different from one other, and so are considered different target nucleic acids. Ezaki also generally teaches multiplex amplification, and notes that multiplex amplification is useful for identifying pathogens (para. 6), and that primer specificity is important in such contexts (para. 19). Multiplex amplification can also be used for rapid detection (para. 20). Thus, with regard to the set of primers described by the combination of Mitsuo in view of Ezaki in the rejection of claim 1 above, it would be prima facie obvious that multiple sets of primers could be developed to amplify multiple targets. This would provide the benefit of being able to more quickly detect if a particular target is present in a sample, which would be particularly useful in diagnostic contexts. Ezaki teaches that multiplex amplification and primer design are well-known in the art (see paras. 77 and 103 of Ezaki in particular, which teach the use of primer design software that would be accessible to the ordinary artisan), and thus developing primers with specific target sequences to target multiple different nucleic acids would have a reasonable expectation of success.
Thus, claim 15 is prima facie obvious over Mitsuo in view of Ezaki.
Conclusion
No claims are currently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to FRANCESCA F GIAMMONA whose telephone number is (571)270-0595. The examiner can normally be reached M-Th, 7-5pm.
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/FRANCESCA FILIPPA GIAMMONA/Examiner, Art Unit 1681
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