Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of Claims
Applicant's preliminary amendment of the instant application, which was originally submitted on 07/19/2023 and later amended on 05/14/2024, is acknowledged by the Examiner. The cancellation of claims 1 – 20 pursuant to the amendment on 05/14/2024 is acknowledged. Claims 21 – 35 were previously examined and restricted in the Office Action dated 12/19/2025.
Election/Restrictions
Applicant’s election without traverse of a combination of oligomers for determining the presence or absence of hepatitis E virus (HEV) i.e., Group I, in the reply filed on 02/19/2026 is acknowledged. Applicant’s election of the amplification oligomer of (a) as SEQ ID NO: 13; amplification oligomer of (b) as SEQ ID NO: 47, which includes the sequence of SEQ ID NO: 25; and the detection probe oligomer as targeting SEQ ID NO: 39 in the reply filed on 02/19/2026 is also acknowledged. Notably, the Response dated 02/19/2026 has set forth claim 28 as being in both Group I and Group II. It is inferred that this is a typographical error and that Applicant meant that Group II is claims 29 – 35, as communicated in the Office Action dated 12/19/2025.
Claims 23 and 24 are drawn to a nonelected species, i.e., a capture probe oligomer of nonelected sequences. The species election of the target-hybridizing sequence of the capture probe oligomer, i.e., claim 23, is hereby withdrawn to expedite prosecution. However, the withdrawal of claim 24 from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim, stands.
Claims 29 – 35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Election was made without traverse in the reply filed on February 19, 2026. Claims 21 – 23 and 25 – 28 are pending and under review.
Priority
Priority is granted to U.S. Provisional Application No. 61865848 filed 08/14/2013 for claims 21 – 23 and 25 – 28 of the instant application. Thus, the U.S. effective filing date of the instant application is 08/14/2013.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/20/2023 and 02/25/2025 have been considered by the Examiner. Notably, 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." Thus, unless the references have been cited by the Examiner on form PTO-892, they have not been considered.
The IDS filed on 11/20/2023 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. References lacking a legible copy have been lined through. Regardless, all references have been considered.
Specification
The use of the term GenBank® on pages 38, 68, and 69, and possibly others in the specification, which is a trade names or a mark used in commerce, have been noted in this application. The term should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, ℠, or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Applicant is required to properly annotate all trade names and/or marks that are present in the specification.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which Applicant may become aware in the specification.
Drawings
The drawings are objected to under 37 CFR 1.84(u)(1), which states "view numbers must be preceded by the abbreviation "FIG.". In the instant case, the view numbers of Figures 1A – 1D are preceded by the word “Figure” instead of the abbreviation “FIG.”.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the Examiner, the Applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 25 and 26 are objected to because of the following informalities:
There is a typographical error in claim 25, lines 15 and 1 on pages 3 and 4, respectively. There is a missing comma after “particularly”, wherein the phrase should read “particularly,”;
There is a typographical error in claim 26, line 2. There is a missing comma after “particularly”, wherein the phrase should read “particularly,”.
Recommended amendments are underlined. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 21 – 23 and 25 – 28 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.
Claims 21 – 23 and 25 – 28 are vague and unclear, which renders the claim indefinite. Line 1 of claim 21 recites “combination of oligomers” and line 2 recites “oligomer combination”. It is not clear if a “combination” refers to the process of mixing or the mixture itself. In other words, is the “combination of oligomers” an active step or the product itself? The presence of multiple very different interpretations of the same claim language renders the claim indefinite. Similar iterations of “combination of oligomers” occur in claims 22, 23, and 25 – 28. For this examination, it will be inferred that the “oligomer combination” refers to the mixture of oligomers itself. However, an appropriate amendment is required. It is recommended that all iterations of a “combination of oligomers” or equivalents thereof be amended to read “set of oligomers”.
Claim 22 recites the limitation "nucleotide analogs" in line 6. There is insufficient antecedent basis for this limitation in the claim. There is no recitation of “nucleotide analogs” in claim 21, upon which claim 22 depends, and so it is not clear the role it plays in the claimed product of claim 22.
The term “about” in claim 25 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 does not define the degree of variability that is encompassed by “about”. This term is subjective and multiple practitioners could have varying opinions on what constitutes “about” any particular value. Thus, the claims that recite “about” are rendered indefinite. It is suggested that every iteration of the term be removed in its current usage.
Claims 25 – 27 recite the phrase “particularly”, which renders the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. The phrase suggests that the limitation is optional or a preferred embodiment, but is unclear from the claim language itself whether that limitation is essential for infringement or an optional feature. See MPEP § 2173.05(d). Additionally, the specification does not define the degree of variability that is encompassed by “particularly”. This term is subjective and multiple practitioners could have varying opinions on what constitutes “particularly” any particular value. Thus, the claims that recite “particularly” are rendered indefinite.
It is noted that any interpretation of the claims set forth above does not relieve Applicant of the responsibility of responding to this Office Action. If the actual interpretation of the claims is different than that posited by the Examiner, additional rejection(s) and art may be applied in a subsequent Office Action.
35 USC § 112(a)
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.
35 USC § 112(a) – Written Description
Claim 22 is 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 purpose of [the written description requirement] is to ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification"); LizardTech Inc. v. Earth Resource Mapping Inc., 424 F.3d 1336, 1345, 76 USPQ2d 1724, 1732 (Fed. Cir. 2005). This requirement is separate and distinct from the enablement requirement. To satisfy the written description requirement for a claimed genus, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention at the time of filing. See In re Reiffin v. Microsoft Corp., 214 F.3d 1342, 1345, 54 USPQ2d 1915, 1917 (Fed. Cir. 2000). “Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement.” See In re Enzo Biochem, Inc. v. Gen–Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002). See also MPEP § 2163.
The written description requirement 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 In re University of California v. Eli Lilly & Co., 119 F.3d 1559, 1566, 43 USPQ2d 1398, 1404 (Fed. Cir. 1997); and Juno Therapeutics, Inc. v. Kite Pharma, Inc., 10 F.4th 1330, 1337, 2021 USPQ2d 893 (Fed. Cir. 2021).
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, the Applicant must describe a sufficient variety of species to reflect the variation within the genus. See In re AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See In re Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." See In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
The Federal Circuit has clarified the application of the written description requirement to inventions in the field of biotechnology. The Court stated that a written description of an invention requires a precise definition, one that defines the structural features of the chemical genus that distinguishes it from other chemical structures. A definition by function does not suffice to define the genus because it is only an indication of what the genus does, rather than what it is. This is because functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Further, the Court held that to adequately describe a claimed genus, an Applicant must describe a representative number of species of the claimed genus, and that one of skill in the art should be able to “visualize or recognize the identity of the members of the genus.” The description needed to satisfy the written description varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology. See In re University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997); In re AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014); In re Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 94 USPQ2d 1161 (Fed. Cir. 2010); and In re Capon v. Eshhar, 418 F.3d at 1357, 76 USPQ2d at 1084.
Claim 22 is drawn to a set of oligomers for determining the presence or absence of hepatitis E virus (HEV) in a sample, wherein nucleotide analogs of the given sequence are included. The claim encompasses a large genus, i.e., any nucleotide analog that is known in the art. The genus grows exponentially larger considering that the analog can be placed at different positions within a given oligomer. In general, this creates an enormous breadth of potential nucleotide analogs that grows exponentially larger when
When there is substantial variation within the genus, as here, one must describe a sufficient variety of species to reflect the variation within the genus to provide a “representative number” of species. The claims are drawn to a large genus that is comprised of numerable nucleotide analogs that could be attached at various positions of an oligomer, yet, the specification has only adequately described, and successfully reduced to practice, a 2’-methoxy backbone nucleotide analog, as in a methoxy substitution at the 2’ position. One of ordinary skill in the art cannot conclude that Applicant was in possession of the numerous nucleotide analogs encompassed by the disclosed genus. Absent the disclosed nucleotide analog, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, each individual nucleotide analog utilized. Thus, it is clear that the breadth of the recited genus in the claim far overreaches the Applicant’s contribution.
In the absence of a representative number of examples, the specification must at least describe the structural features that are required for the claim function. In the instant case, the specification should explain the property of the detection probe oligomer, i.e., the sequence, that must be retained that would still allow amplification of the target nucleic acid with any nucleotide analog. However, the specification fails to describe any substantive structural limitations as to establish how the primers could still amplify the target nucleic acid if they were mismatched. At best, the specification contemplates the use of BLAST to identify functional homologs based on sequence homology. However, this is not sufficient to describe members of the claimed genus because such methods access online databases that are continually being updated as sequencing technology improves. As a result, they are not a static source of information. Therefore, one having ordinary skill in the art would readily appreciate that relying on a non–patent source that is continuously subject to change as a means to identify members of the claimed genus does not sufficiently meet the written description requirement.
The art teaches that nucleic-acid based assays rely heavily on efficient hybridization of nucleotides to the target sequence, wherein mismatches between the nucleotides and target sequence hinder the system. For example, Christopherson, C., et. al., (Nucleic Acids Research, (25)3, 654–658; Published February 1997), hereby Christopherson, teaches that internal primer-template mismatches have reduced amplification efficiency in RT-PCR experiments (page 654, left column). It is further taught that while two to four mismatches in the primer-template duplex can be tolerated without significant effects on RT-PCR, the presence of five or six mismatches within 28 and 30 base primers significantly reduced the PCR product yield by 22- and 100-fold, respectively, relative to the template (page 654, abstract). Furthermore, Stadhouders, R., et. al., (The Journal of molecular diagnostics: JMD, 12(1), 109–117; Published January 2010), hereby Stadhouders, teaches that a single mismatch in the primer-template can have severe impacts on PCR amplification (page 109, left column). Day, J. P., et. al., (Nucleic acids research, 27(8), 1810–1818; Published April 15, 1999), hereby Day, teaches that no nucleotide analog functions as a universal base capable of generalized conversion (page 1814, left column, bottom paragraph). Thus, when taken with the teachings of Christopherson, Stadhouders, and Day, one having ordinary skill in the art would readily appreciate that sequence homology alone cannot serve as the basis to describe members of the genus that have the recited function, especially towards mismatched primers during PCR, wherein the nucleotide analog must be optimized for a particular sequence.
In summary, these examples teach that the function of nucleic acid-based assays is heavily dependent on the hybridization of the primers, wherein mismatches are not well tolerated and greatly reduce the efficiency. Thus, while Applicant has described a species within the genus recited, and the art may provide more, each genus is very large and would encompass structures that cannot be visualized from the prior art or instant disclosure. One having ordinary skill in the art cannot determine the structures encompassed by the claimed genera. Thus, the described species cannot be considered representative of the entire recited genus.
Overall, the claims as currently written are not adequately described and one of ordinary skill in that art would readily appreciate that Applicant was not in possession of the claimed genera at the time of filing. At present, it is recommended that the claims remove the recitation of “nucleotide analogs”.
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 21, 22, and 25 – 28 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claims recite “SEQ ID NO: XX, including RNA equivalents and DNA/RNA chimerics thereof”. The RNA equivalent of the recited SEQ ID NO, i.e., the primers of the claims, are a natural product as they are drawn to a naturally occurring sequence from the viral genome. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception for the reasons set for below.
The claims are drawn to a composition or kit for determining the presence or absence of influenza B in a sample. As such, the claimed method, which is drawn to a process, falls into one of the four categories of patent eligible subject matter (i.e., process, machine, manufacture, or composition of matter) (Step 1: YES). The claims are drawn to a judicial exception of a natural phenomenon, specifically a product of nature (Step 2A, Prong One: YES). Claim 21 recites different iterations of “includes at least the sequence of SEQ ID NO: 26, including RNA equivalents and DNA/RNA chimerics thereof”. The claims include RNA equivalents that differ by 0 nucleotides, which encompasses naturally occurring sequences. This rejection affects all dependent claims, i.e., claims 22 and 25 – 28. However, there are similar iterations of “or an RNA equivalent” in claims 22 and 25 – 27 in relation to hepatitis E virus (HEV), which is an RNA virus. Thus, RNA equivalents with the same sequence as the coding strand for the virus would be fragments of the natural RNA viral genome. Laws of nature and natural phenomena, as identified by the Courts, include naturally occurring principles/relations and nature-based products that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature. The law of nature and natural phenomenon exceptions reflect the Court's view that the basic tools of scientific and technological work are not patentable, because the "manifestations of laws of nature" are "part of the storehouse of knowledge," "free to all men and reserved exclusively to none."
Overall, the claims as a whole are not limited to a particular RNA equivalent and constitutes a generic molecule with the same sequence as the viral genome. There is no indication in the specification that the nucleic acids claimed here have any structural or functional characteristics that differ from the naturally occurring nucleic acids. Accordingly, the nucleic acids are a natural phenomenon and directed to a judicial exception. There are no additional elements recited in the claims that integrate the judicial exception into a practical application (Step 2A, Prong Two: NO). The claimed invention does not use or apply the judicial exception in a meaningful way to contribute to an inventive concept or amount to significantly more than the judicial exception (Step 2B: NO). Thus, the claims fail the subject matter eligibility test (Steps 1 and 2A, Prong One: YES; Steps 2A, Prong Two and 2B: NO) and are not eligible subject matter. See MPEP § 2106 and 2173.05(q). See also In re Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576, 589-91, 106 USPQ2d 1972, 1978-79 (2013) and In re University of Utah Research Foundation v. Ambry Genetics Corp., 774 F.3d 755, 761, 113 USPQ2d 1241, 1244 (Fed. Cir. 2014). At present, it is recommended that the claims remove the recitation of “or an RNA equivalent” in claims 21, 22, and 25 – 27.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 21 – 23 and 25 – 28 are rejected under 35 U.S.C. 103 as being unpatentable over, Narayanan, J. and Hill, V. (U.S. Patent No. 7709626 B2; Published May 4, 2010; Cited in Applicant’s IDS on November 20, 2023 as U.S. Patent Cite No. 3), hereby Hill, in view of Enouf, V. et. al., (Journal of medical virology, 78(8), 1076–1082; Published June 20, 2006; Cited in Applicant’s IDS on November 20, 2023 as Non-Patent Literature Cite No. 3), hereby Enouf; as evidenced by Buck, G. A., et. al., (BioTechniques, 27(3), 528–536; Published 09/1999), hereby Buck, GenBank® Accession Code No. AB074918.2 (Submitted November 27, 2001; Cited in Applicant’s IDS on November 20, 2023 as Non-Patent Literature Cite No. 8), hereby GenBank ‘918, and GenBank® Accession Code No. AB593690.1 (Published 10/22/2011), hereby GenBank ‘069.
Narayanan teaches universal primers for the detection and amplification of nucleic acid molecules, including those from Hepatitis E virus (HEV) sequences, that are attached to the end of an appropriate sequence-specific primer, wherein instant SEQ ID NO: 16 has 100% sequence similarity to the sequence taught by SEQ ID NO: 26, which is the forward primer for amplification of HEV; and instant SEQ ID NO: 25, and thus, instant SEQ ID NO: 47, have 100% sequence similarity to the sequence taught by SEQ ID NO: 27, which is the reverse primer for amplification of HEV (abstract; column 7, lines 30 – 33; column 12, lines 28 – 32 and lines 45 – 58; column 26, lines 33 – 38; column 27, lines, 27 – 29; see sequence alignment as reproduced below on the top and bottom, respectively), as required in instant claims 21 and 22. The primers are generally at least 9 nucleotides in length, but longer primers that are 10, 12, 15, 20, 25, 30 or 50 nucleotides or more in length are often selected to obtain greater specificity to a target sequence (column 11, lines 41 – 59; column 12, lines 28 – 32; column 15, lines 48 – 54; claim 20), as required in instant claims 21 and 22. Additionally, modified bases, modified sugar moieties, and modified phosphate backbones, i.e., nucleotide analogs, can be included to modify the primer at any position on its structure (column 10, lines 66 and 67; column 11, lines 1 – 21), as broadly defined in instant claim 22. Narayanan goes on to teach an anchored/immobilized universal primer that can be employed as a capture probe to allow for amplification and detection of sample nucleic acid molecules when incubated with appropriate primers that are covalently attached to a surface (column 20, lines 7 – 17; column 21, lines 44 – 49), as defined in instant claim 23. It is further taught that one or more sequence-specific primers for a particular viral pathogen, i.e., HEV, may be packaged together as a kit (column 4, lines 15 – 23; column 18, lines 59 – 63), as
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defined in instant claims 26 and 28.
Narayanan does not explicitly teach the detection probe oligomer comprising a target-hybridizing sequence that is from 14 – 28 nucleotides in length and configured to specifically hybridize to a target sequence contained with instant SEQ ID NO: 39, as required in instant claims 21, 22, and 27; and that the amplification oligomer of (a) in claim 21 comprise from 14 to 20 nucleotides of instant SEQ ID NO: 13, as defined in instant claim 25.
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Enouf teaches an HEV primer sequence that readily detects any of the four major genotypes of HEV, wherein one of the primers, i.e., TaqHEV-R, is 18 nucleotides in length with the sequence of 5’- CTGAGAATCAACCCGGTCAC-3’ (page 1077; left column, first paragraph; page 1079, table 2), which reads on a hybridizing sequence that is 14 nucleotides in length and configured to hybridize instant SEQ ID NO: 39 (see alignment results as reproduced below), as required in instant claims 21 and 22. The reactions were performed in a final volume of 15 µL with 0.3 µM of each HEV-specific primer, which reads on the numerous molecules of the detection probe oligomer designed to hybridize instant SEQ ID NO: 39 in instant claim 27. Of note, Enouf teaches that the designed probe used for the detection of HEV was directed to a highly conserved region within open reading frame (ORF) 2 of the genome, i.e., 5250 – 5269, in the middle of the two designed primers, wherein the probe was labeled with 6-carboxyfluorescein (FAM) at the 5’ end and 6 carboxy-tetramethylrhoda-mine (TAMRA) at the 3’ end (page 1079, right column and table 2).
Buck provides evidence for the equivalence of primers. It is taught that 69 manually designed primers submitted by 39 different labs towards a 300 bp test sequence functioned extremely well in comparison to a panel of 95 synthesized primers that were used as controls (page 530, first and third columns; page 533, first column). Buck teaches that the primers ranged in length from 15 – 40 nucleotides, wherein the optimal range was 18 – 24 nucleotides (page 529, table 1), It is explicitly stated by Buck that, “[T]he results of the empirical sequencing analysis were surprising in that nearly all of the primers yielded data of extremely high quality.” Thus, Buck provides direct evidence that all primers would be expected to function, and in particular, all primers selected according to the ordinary criteria would function well. This clearly shows that every primer would have a reasonable expectation of success when the target sequence is known. The target sequence of the HEV genome is known in the art, as taught by GenBank ‘918 and required by instant claims 21 – 24 and 26 – 28. To be specific, instant SEQ ID NOs: 4, 13, 27, 39, and 47 are all taught by GenBank ‘918 (see alignment results as reproduced below for instant SEQ ID NOs: 4, 13, 27, 39, and 47, in that order, wherein y and w in instant SEQ ID NO: 4 denotes t/u or c and a or t/u, respectively; and s in instant SEQ ID NO: 47 denotes a g or c nucleotide [See MPEP § 2422]). While GenBank ‘918 teaches 20 out of 21 of the nucleotides SEQ ID NO: 42, it is missing a g at the end of the sequence, equating to a query match that is 95.2% instead of 100% (see alignment results as reproduced below on the top). However, GenBank ‘069, which is also HEV genomic RNA, teaches the full target sequence of SEQ ID NO: 42 (see alignment results as
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reproduced below on the bottom).
Since all of the target genomes are known in the art, it would have been prima facia obvious to a person having ordinary skill in the art to design primers for the sequences disclosed by SEQ ID NOs: 13, 25, 39, and 47 that have variable lengths with a reasonable expectation of success, as disclosed in instant claims 21, 22, and 25. Of note, SEQ ID NO: 63 comprises S EQ ID NO: 13, wherein SEQ ID NO: 13 consists of SEQ ID NO: 26. To be more specific, SEQ ID NO: 26 is found within SEQ ID NO: 13, whereas SEQ ID NO: 63 is slightly longer than SEQ ID NO: 13, i.e., 20 nucleotides versus 23 nucleotides, respectively. In turn, SEQ ID NO: 13 reads on instant claim 21 and, thus, GenBank ‘918 teaches SEQ ID NOs: 26 and 63. Moreover, since the target genomes of the capture probe oligomers are known in the art, it would have been prima facia obvious to a person having ordinary skill in the art to design probes for the sequences disclosed by SEQ ID NOs: 4 and 42 with a reasonable expectation of success, as required in instant claims 23.
Narayanan, Enouf, Buck, GenBank ‘918, and GenBank ‘069 are considered to be analogous to the claimed invention because are all drawn to primer design. Based on prior art teachings, it would have been obvious to a person having ordinary skill in the art to design primers as taught by Buck in view of the HEV genome as taught by GenBank ‘918 and GenBank ‘069 and using the HEV primer sequences disclosed in Narayanan and Enouf. This obviousness is mainly owed to Narayanan and Enouf teaching methods for detecting HEV in a sample using primers. Therefore, it would have been obvious to a person having ordinary skill in the art to have combined the teachings of Narayanan, Enouf, Buck, GenBank ‘918, and GenBank ‘069 before the effective filing date of the claimed invention with a reasonable expectation of success to provide a highly sensitive and specific tool for accurate quantification of major genotypes of HEV virus, even when there are very low HEV loads (Enouf; page 1081, right column, second and fourth paragraph). All the claimed elements were known in the prior art. It would have been obvious for a person having ordinary skill in the art to have combined the elements as claimed by known methods with no change in their respective functions. The combination would have yielded nothing more than predictable results to one having ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415–421, 82 USPQ2d 1385, 1395–97 (2007) and MPEP § 2143(A) and 2143.02.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP § 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 21 – 23 and 25 – 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 18 of U.S. Patent No. 10047406, hereby ‘406, in view of Buck, G. A., et. al., (Design strategies and performance of custom DNA sequencing primers. BioTechniques, 27(3), 528–536; Published September 1999), hereby Buck; and GenBank® Accession Code No. AB074918.2 (Submitted November 27, 2001; Cited in the USPTO Office Action for U.S. Patent Application No. 16015539 and in Applicant’s IDS on November 20, 2023 as Non-Patent Literature Cite No. 4), hereby GenBank.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to a set of oligomers, and a kit thereof, defined by their hybridizing sequence for determining the presence or absence of Hepatitis E Virus (HEV) in a sample, wherein there is a detection probe oligomer configured to target a sequence within SEQ ID NO: 39 (see instant claims 21 and 28 versus claims 1 and 15 of ‘406).
Buck provides direct evidence that all primers would be expected to function, and in particular, all primers selected according to the ordinary criteria would function well (whole document; see page 529, table 1). This clearly shows that every primer would have a reasonable expectation of success when the target sequence is known. GenBank teaches the complete HEV genomic sequence, wherein SEQ ID NO: 47, and, thus, SEQ ID NO: 25, and SEQ ID NO: 39 are found within the described genomic sequence. Thus, the whole HEV sequence is known and it would have been prima facia obvious for one of ordinary skill in the art to prepare different primers from ‘406 to achieve the instant invention based on the complete sequence of GenBank. Notably, claim 17 of ‘406 is drawn to a method of using the set of oligomers as described in the instant claims.
Claims 21 – 23 and 25 – 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 19 of U.S. Patent No. 10053742, hereby ‘742, in view of Buck, G. A., et. al., (BioTechniques, 27(3), 528–536; Published September 1999), hereby Buck; and GenBank® Accession Code No. AB074918.2 (Submitted November 27, 2001; Cited in the USPTO Office Action for U.S. Patent Application No. 16015539 and in Applicant’s IDS on November 20, 2023 as Non-Patent Literature Cite No. 4), hereby GenBank.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to a set of oligomers, and a kit thereof, that are defined by their hybridizing sequence for determining the presence or absence of Hepatitis E Virus (HEV) in a sample, wherein there is a detection probe oligomer configured to target a sequence within SEQ ID NO: 39 (see instant claim 21 and 28 versus claims 2, 3, and 18 of ‘742).
Buck provides direct evidence that all primers would be expected to function, and in particular, all primers selected according to the ordinary criteria would function well (whole document; see page 529, table 1). This clearly shows that every primer would have a reasonable expectation of success when the target sequence is known. GenBank teaches the complete HEV genomic sequence, wherein SEQ ID NO: 47, and, thus, SEQ ID NO: 25, and SEQ ID NO: 39 are found within the described genomic sequence. Thus, the whole HEV sequence is known and it would have been prima facia obvious for one of ordinary skill in the art to prepare different primers from ‘742 to achieve the instant invention based on the complete sequence of GenBank.
Claims 21 – 23 and 25 – 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 18 of U.S. Patent No. 10815541, hereby ‘541, in view of Buck, G. A., et. al., (BioTechniques, 27(3), 528–536; Published September 1999), hereby Buck; and GenBank® Accession Code No. AB074918.2 (Submitted November 27, 2001; Cited in the USPTO Office Action for U.S. Patent Application No. 16015539 and in Applicant’s IDS on November 20, 2023 as Non-Patent Literature Cite No. 4), hereby GenBank.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to a set of oligomers, and a kit thereof, defined by their hybridizing sequence for determining the presence or absence of Hepatitis E Virus (HEV) in a sample, wherein there is a detection probe oligomer configured to target a sequence within SEQ ID NO: 39 (see instant claims 21 and 28 versus claims 1 and 10 of ‘541, respectively).
Buck provides direct evidence that all primers would be expected to function, and in particular, all primers selected according to the ordinary criteria would function well (whole document; see page 529, table 1). This clearly shows that every primer would have a reasonable expectation of success when the target sequence is known. GenBank teaches the complete HEV genomic sequence, wherein SEQ ID NO: 47, and, thus, SEQ ID NO: 25, and SEQ ID NO: 39 are found within the described genomic sequence. Thus, the whole HEV sequence is known and it would have been prima facia obvious for one of ordinary skill in the art to prepare different primers from ‘541 to achieve the instant invention based on the complete sequence of GenBank. Notably, claim 11 of ‘541 is drawn to a method of using the set of oligomers as described in the instant claims.
Claims 21 – 23 and 25 – 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 20 of U.S. Patent No. 11572596, hereby ‘596, in view of Buck, G. A., et. al., (BioTechniques, 27(3), 528–536; Published September 1999), hereby Buck; and GenBank® Accession Code No. AB074918.2 (Submitted November 27, 2001; Cited in the USPTO Office Action for U.S. Patent Application No. 16015539 and in Applicant’s IDS on November 20, 2023 as Non-Patent Literature Cite No. 4), hereby GenBank.
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to a set of oligomers, and a kit thereof, defined by their hybridizing sequence for determining the presence or absence of Hepatitis E Virus (HEV) in a sample, wherein there is a detection probe oligomer configured to target a sequence within SEQ ID NO: 39 (see instant claims 21 and 28 versus claims 1, 7, and 10 of ‘596, respectively).
Buck provides direct evidence that all primers would be expected to function, and in particular, all primers selected according to the ordinary criteria would function well (whole document; see page 529, table 1). This clearly shows that every primer would have a reasonable expectation of success when the target sequence is known. GenBank teaches the complete HEV genomic sequence, wherein SEQ ID NO: 47, and, thus, SEQ ID NO: 25, and SEQ ID NO: 39 are found within the described genomic sequence. Thus, the whole HEV sequence is known and it would have been prima facia obvious for one of ordinary skill in the art to prepare different primers from ‘596 to achieve the instant invention based on the complete sequence of GenBank. Notably, claim 11 of ‘596 is drawn to a method of using the set of oligomers as described in the instant claims.
Conclusion
Claims 21 – 23 and 25 – 28 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Hallie N. Pennington, Ph.D. whose telephone number is (571)272-6781. The Examiner can normally be reached M-Th 7:30-5:30 ET.
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/HALLIE N. PENNINGTON, PH.D./Examiner, Art Unit 1671
/Michael Allen/Supervisory Patent Examiner, Art Unit 1671
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