DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed January 7, 2026. Currently, claims 1-2, 4, 6, 8, 10, 12, 17-20, 22-29 are pending. Claims 1-2, 4, 6, 8, 10, 12, 18-20, 24-29 have been withdrawn as drawn to non-elected subject matter.
All arguments have been thoroughly reviewed but are deemed non-persuasive for the reasons which follow. This action is made FINAL.
Any objections and rejections not reiterated below are hereby withdrawn.
Election/Restrictions
Applicant's election without traverse of Group II and targets SEQ ID NO: 4-6. Claims 17, 22-23 in the paper filed August 20 2025 is acknowledged.
The examiner has required restriction between subcombinations usable together. Applicant elected a subcombination, namely and targets SEQ ID NO: 4-6. Rejoinder of the additional targets depending on the elected targets will be considered once allowable subject matter is identified. Applicant is advised that if any claim presented in a continuation or divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application.
Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
The requirement is still deemed proper and is therefore made FINAL.
Priority
This application claims priority is a 371 of PCT/FI2020/050766, filed November 16, 2020 and claims priority to foreign application FINLAND 20195975, filed November 15, 2019.
Drawings
The drawings are acceptable.
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 17, 22-23 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. Based upon an analysis with respect to the claim as a whole, the rejected claim(s) do not recite something significantly different than a judicial exception. The rationale for this determination is explained below:
Briefly, claims 17, 22-23 are rejected because these claims are drawn to a oligonucleotide primers and probes. The oligonucleotide probe includes a fluorophore label. Claim 22-23 are directed to kits and kits comprising additional PCR reagents.
Claim 17, 22-23 are directed to nucleic acid fragments from the Encepholitozoon intestinalis, cuniculi and hellem genomes, i.e. known naturally occurring nucleic acids. Such isolated nucleic acid molecules, that are identical to fragments of naturally occurring nucleic acid molecules are not patent eligible subject matter, i.e. they are judicial exceptions to patentable subject matter.
Claim 23 further requires reagents including polymerase, buffers, salts, nucleotides. Given the broadest reasonable interpretation, these additional reagents are enzymes that are naturally occurring.
The claims require that the isolated nucleic acid probe includes a fluorophore detectable label.
MPEP 2106.04(b)(II) discusses products of nature. The MPEP specifically discusses DNA, primers and probes. The isolated DNA of Myriad and the primers of Ambry Genetics were described as products of nature by the courts. Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2116-17, 106 USPQ2d 1972, 1979 (2013); University of Utah Research Foundation v. Ambry Genetics, 774 F.3d 755, 758-59, 113 USPQ2d 1241, 1243 (Fed. Cir. 2014). The MPEP further states the “product of nature exceptions includes both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart. See, e.g., Ambry Genetics, 774 F.3d at 760, 113 USPQ2d at 1244 ("Contrary to Myriad's argument, it makes no difference that the identified gene sequences are synthetically replicated. As the Supreme Court made clear, neither naturally occurring compositions of matter, nor synthetically created compositions that are structurally identical to the naturally occurring compositions, are patent eligible.").” The Federal Circuit in Ambry Genetics reviewed “[t]he Supreme Court held ineligible claims directed to segments as short as 15 nucleotides, the same length as the primer claims at issue here, suggesting that even short strands identical to those found in nature are not patent eligible. Compare ’492 patent col. 170 ll. 32–38, with ’282 patent col. 153 ll. 66–67.”
In the instant case, the claims, embrace naturally occurring primers that are identical to naturally occurring gene fragments and clearly read on nature-based products that themselves do not exhibit markedly different characteristics from the naturally occurring gene. See e.g. Myriad in which one claim at issue was drawn to “[a]n isolated DNA having at least 15 nucleotides [an isolated DNA coding for a BRCA1 polypeptide having the amino acid sequence of SEQ ID NO: 2] (Myriad at 2113). The Court recognized that this claim, if valid, would have given Myriad exclusive right to isolate any strand of 15 or more nucleotides of an individual’s BRCA1 gene (paragraph bridging 2113 and 2114). This is directly analogous to the instant situation wherein Applicant’s claims cover probe and primer molecules that are fragments of a naturally occurring Encepholitozoon intestinalis, cuniculi and hellem genome sequence. The Court held that “[a] naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated”, and that “Myriad’s claims are not saved by the fact that isolating DNA from the human genome severs the chemical bonds that bind gene molecules together” (page 2118). The Court found that while Myriad had located and sequenced an important gene, Myriad had not created anything, and that “separating that gene from its surrounding genetic material is not an act of invention” (page 2118). Consistent with the findings of the Court in Myriad, the Office finds that the primers and probe molecules embraced by the instant clams are not patent eligible compositions of matter regardless of whether or not they are isolated from the genome. The Guidelines indicate that a change in biological function or activity maybe a characteristic of an isolated product that can provide a marked difference sufficient to distinguish over a naturally occurring product. However, in this case, as in the Ambry case, the function of the nucleic acids is the same function as the relevant portion of the naturally occurring sequence. Just as in nature, primers utilize the innate ability of DNA to bind to itself.
The claims have also been amended to add a probe detectably labeled with a fluorophore. Having established that the claims include a naturally occurring product, namely the primer pairs, that is a judicial exception, it must now be determined whether or not the claims recite an element or combination of elements that amount to significantly more than that exception, and whether those additional elements also amount to significantly more for the other claimed exception(s), which ensures that the claim does not have a preemptive effect with respect to any of the recited exceptions. To determine whether a claim that includes a nature-based product limitation recites a “product of nature” exception, an analysis is performed in which it is first determined if a claim includes a nature-based product that has markedly different characteristics from the corresponding naturally occurring product, and if it does not, then it is determined whether or not other elements of the claim are sufficient to ensure that the claim as a whole amounts to significantly more than the exception itself (see the Interim Guidance on Patent Subject Matter Eligibility published 12/16/2014 in the Federal Register at pages 74618-74633). In order to be markedly different the claimed product must possess at least one characteristic that is different from that of the counterpart. The addition of a fluorophore labeled probe with no particular nucleic acid sequence is not unique. At the time the invention was made, adding labeled probes to kits for detecting parasites was routine.
Further, claims 22-23 recite additional elements, i.e. buffers, reaction tubes, contains, vials. None of these limitations provides any significant addition to the judicial exceptions already claimed that would prevent the claims from having a pre-emptive effect on the use of the judicial exception. The presence of a kit “tube" in a composition comprising a nucleic acid is entirely conventional and does not represent a modification that amounts to something significantly more than the judicial exception.
The fact that these natural products are organized into a kit with an intended use adds nothing to the judicial exceptions that would distinguish them from the naturally occurring material. The kit must be considered in the context of whether or not the combination can provide some way of ensuring it does not limit the public’s access to the naturally occurring material. Therefore, the claims are properly rejected under 35 USC 101 as being drawn to patent-ineligible subject matter.
Response to Arguments
The response traverses the rejection. The response asserts the rejection is obviated by amending the claim to require a fluorophore labeled probe. The response argues that a fluorescent label is markedly different than a naturally occurring nucleic acid and the inclusion of the label in the composition integrates the judicial exception.
This argument has been considered but is not convincing because the claim recites a naturally occurring nucleic acid pair of primers. In addition to the primer pair, the “additional elements” are a generic probe labeled with a fluorophore. This labeled probe is not unique. It is routine and conventional to place labeled probes in kits for detecting parasites. Adding “well understood” labeled probes to kits was routinely combined with other nucleic acid sequences.
Even when considering the composition as a whole, the labeled probe does not interact with the naturally occurring primer pairs in the composition. The probes and primers do not change in structure because they are in solution together. The composition does not attain a new or different structure by being in composition together and the intended use of the composition does not change the nature of the composition. The primer pairs will still anneal to a target. Thus, there is no change in structure to form a new property of the composition. Merely providing a labeled probe and naturally occurring primer pairs in a composition does not change the property or function of the individual elements or make the mixture itself markedly different.
Thus, for the reasons above and those already of record, the rejection is maintained.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 17, 22-23 are rejected under 35 U.S.C. 103(a) as being unpatentable over Wolk et al. (J. of Clinical Microbiology, Vol. 40, No. 11, pages 3922-3928, November 2002) in view of Pirestani et al. (Infection, Genetics, and Evolution, No. 20, pages 495-499, 2013).
Wolk teaches primers and probes for real-time PCR method detection of E. Intestinalis, E. cuniculi and E. hellem (abstract). Wolk teaches primers and fluorescence probes were designed to amplify a 268-bp region of the 16S rRNA gene of E. Intestinalis, E. cuniculi and E. hellem (page 2923, col. 2). The reverse primer of Wolk aligns with SEQ ID NO: 4-6 (see below).
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Wolk does not teach a primer pair consisting of SEQ ID NO: 22-27.
Pirestani teaches isolating DNA from samples and amplifying the samples with specific primers. Pirestani teaches the genotypes of internal transcribed spacer (ITS) of the rRNA gene were determined for all isolates (abstract). Pirestani teaches the sequences of the isolates from the study are accessible under GenBank Accession Nos. JF792394-98, which comprise SEQ ID NO: 22-27.
SEQ ID NO: 24 is embedded within JF792394.
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SEQ ID NO: 27 is embedded within JF792394.
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Therefore, it would have been prima facie obvious to a skilled artisan at the time of filing to have designed primers and probes to known sequences (such as the sequences disclosed in the above references) with a high expectation of success. Pirestani teaches the sequences E. Intestinalis, E. cuniculi and E. hellem isolates from the study are accessible under GenBank Accession Nos. JF792394-98. To design such primers constituted routine and conventional optimization at the time of filing. See In re Aller, 220 F.2d 454, at 456 (CCAP 1955) (“where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.”). The art is replete with references that describe how to design and optimize primers and probes for PCR applications. For example, Pirestani teaches sequencing, aligning sequences and comparing the sequences. Wolk teaches designing primers and probes to known GenBank sequences. The art teaches many commercially available programs, such as Primer3Plus online program to design primers and probes to known sequences. In other words, the art proves specific guidance and parameters to optimize primer, probe and PCR assay design to yield optimal results; thus, designing PCR assays for particular applications constitutes well-known routine optimization. The well-known Primer3 computer program can design primers and probes for PCR applications In addition, selection of specific oligonucleotides for specific Tm represents routine optimization with regard to sequence, length and composition of the oligonucleotide. As noted in In re Aller, 105 USPQ 233 at 235, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Routine optimization is not considered inventive and no evidence has been presented that the primer selection performed was other than routine, that the products resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. Thus, the instant sequences are clearly a functional homologues of the above similar primers based on the known sequences. This is supported by In Re Deuel, 34 USPQ 2d 1210 (Fed. Cir. 1995), in which the Court of Appeals for the Federal Circuit stated that (emphasis added).
Response to Arguments
The response traverses the rejection. The response asserts the claims require forward and reverse primers of parts a-c “consisting of” recited nucleotide sequences. This argument has been reviewed but is not convincing. The claims require only one
This argument has been considered but is not convincing because the claims only require one of the primer pairs and not all three pairs. Thus, the claims minimally requires SEQ ID NO: 22 and 23 or SEQ ID NO; 24 and 25 or SEQ ID NO: 26 and 27.
The response argues the art would not have led an ordinary skilled artisan to the particular primer sequences specified in the claims. The response notes that the reverse primers of SEQ ID NO: 23, 25 and 27 are 64 bp downstream of Wolk’s target sequence. Applicant's arguments were not persuasive, because, as noted in MPEP 2143, explicit motivation is not required to establish a prima facie case of obviousness. This section of the MPEP states that one rationale that may be used to establish a prima facie case of obviousness is "choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success". In this case, at the time of the invention, as evidenced by the teachings of Pirestani and Wolk, there was a recognized need in the art for multiplex PCR methods for detecting intestinal parasites of E. intestinalis, E. cuniculi, and E. hellen based on the detection of the 18S rRNA sequences. Since Wolk identified 18S sequences as being suitable for primer design, and since Lowe disclosed primer design rules and a program for automating primer design applying said rules, the ordinary artisan would have been presented with a finite number of predictable solutions to the problem of developing primers and probes for amplifying and detecting E. intestinalis, E. cuniculi, and E. hellen. Based on the teachings of Lowe concerning primer design rules and software applying said rules, the ordinary artisan would have had a reasonable expectation of success in pursuing these potential solutions. It is also noted that applying the conventional primer design methods disclosed by Lowe would present the ordinary artisan with a finite number of possible primer and probe sequences.
The response argues that designing primers for diagnostic assays is neither routine nor predictable. The response asserts that it takes several attempts to identify optimal combinations of oligos that can produce high performance results. The presence of some experimentation that is routine is not indicia of non-obviousness. As noted in In re Aller, 105 USPQ 233 at 235, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. Routine optimization is not considered inventive and no evidence has been presented that the primer selection performed was other than routine, that the products resulting from the optimization have any unexpected properties, or that the results should be considered unexpected in any way as compared to the closest prior art. Thus, the instant sequences are clearly a functional homologues of the above similar primers based on the known sequences. This is supported by In Re Deuel, 34 USPQ 2d 1210 (Fed. Cir. 1995), in which the Court of Appeals for the Federal Circuit stated that (emphasis added).
The response argues that SEQ ID NO: 22-27 can detect Encephalitozoon with high specificity including use in multiplexing. The response argues that computer program provides no guidance whether the oligonucleotides could achieve such a high level of specificity. This argument has been reviewed but is not persuasive. It appears applicant is arguing secondary considerations. First, the claims do not require any multiplexing. Thus, the arguments are not commensurate in scope with the claims. Second, the primers have not been compared to the closest prior art to show unexpected results. MPEP 716.01(c): “Objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results…[t]he arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results.” The response does not compare the primers consisting of SEQ ID NO: 22-27 to any of the prior art primers to demonstrate the claimed primers are superior to the primers taught in the art. There is no evidence of unexpected results. Thus for the reasons above and those already of record, the rejection is maintained.
Conclusion
No claims allowable over the art.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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, Wu-Cheng (Winston) Shen can be reached on (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
February 19, 2026
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