Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Status of Claims
2. Applicant's preliminary amendment of the instant application, which was originally submitted on 04/28/2023 and later amended on 09/20/2023, is acknowledged by the Examiner. The previous cancellation of claims 3 – 11, 18 – 24, 27, 29 – 39, 41, 46, 48 – 57, 60 – 62, 64 – 66, 68, 71, 73, and 75 – 80 pursuant to the amendment on 09/06/2023 is acknowledged. Claims 1, 2, 12 – 17, 25, 26, 28, 40, 42 – 45, 47, 58, 59, 63, 67, 69, 70, 72, and 74 were previously examined and restricted in the Office Action mailed on 11/14/2025.
Election/Restrictions
3. Applicant’s election without traverse of the influenza B region 1 primer set, i.e., the sixth primer set, in the reply filed on 01/08/2026 is acknowledged. This election includes the first and second influenza B region 1 primers with SEQ ID NOs: 72 and 106, which comprise SEQ ID NOs: 91 and 86 or 87, respectively; influenza B region 1 probe with SEQ ID NO: 122 that comprises SEQ ID NO: 89; and influenza B target capture oligonucleotide with SEQ ID NO: 111.
Claims 13, 16, 25, 47, 58, and 59 have been canceled pursuant to the amendment filed on 01/08/2026. Claims 1, 2, 12, 14, 15, 17, 26, 28, 40, 42 – 45, 63, 69, 70, 72, and 74 have been amended to reflect the election of the influenza B region 1 primer set. Claims 81 – 94 are new and read on the election, but the matter is found in the claims previously presented. No claims are withdrawn from consideration as being drawn to a nonelected invention. The claims are examined as they read on the election. Election was made without traverse in the reply filed on 01/08/2026. Thus, claims 1, 2, 12, 14, 15, 17, 26, 28, 40, 42 – 45, 63, 67, 69, 70, 72, 74, and 81 – 94 are pending in this application and are under examination.
Priority
4. The instant application is a National Stage Entry of International Patent Application No. PCT/US2021/057223 filed on 10/29/2021 and also claims priority to United States Provisional Application No. 63/107779 filed on 10/30/2020. Priority is granted to the U.S. Provisional Application for the claims presently under examination.
Information Disclosure Statement
5. The information disclosure statements (IDS) submitted on 09/29/2023 and 07/31/2025 have been considered by the Examiner. However, the IDS submitted on 09/29/2023 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. All references have been considered, except where lined through. Additionally, 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.
Specification
6. The use of the terms TaqMan™ on page 15; Black Hole Quencher™ on page 15; BHQ™ on page 15; Tamra™ on page 15; KingFisher™ on page 73, and possibly others in the specification, which are trade names or a marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, ℠, or ® following the terms. 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. Note that the terms outlined above are merely examples. Applicant is required to properly annotate all trade names and/or marks that are present in the specification.
7. 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
8. No drawings were present at the time of this Office Action.
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;
the date of creation; and
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 – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). The listing of the poly A sequence, poly T sequence, and polyT-polyA sequence and the associated formula in paragraph 040 of the instant specification is not a proper disclosure of the sequence. This affects the listing of the TnAm sequence in claims 63 and 92 as well.
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 sequence identifiers, 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.
Claim Objections
9. Claims 1, 2, 63, 69, 74, 86, 89, 92, and 93 are objected to because of the following informalities:
There is a grammatical error in claim 1. A conjunction should be added before moving into part (i) of the claim. It is recommended that the phrase read “…Influenza B target nucleic acid, wherein”;
In claims 2 and 93, the acronym “SARS-CoV-2” is recited, but not defined in the claim. An acronym should be defined the first time it appears in an independent claim or in the group of claims under an independent claim. For the purposes of examination, “SARS-CoV-2” is interpreted to mean “severe acute respiratory syndrome coronavirus 2”, as defined in the specifications;
There is a typographical error in claim 2(c)(i). An “a” is missing in the sentence, wherein the phrase should read “comprising a target”;
There is a grammatical error in claim 2(d). A conjunction should be added before moving into part (i) of the claim. It is recommended that the phrase read “…Influenza A target nucleic acid, wherein”;
There is a typographical error in claim 2(d)(ii). An “or” is missing in the sentence, wherein the phrase should read “SEQ ID NO: 18 or an RNA”;
There is a grammatical error in claim 2(e). A conjunction should be added before moving into part (i) of the claim. It is recommended that the phrase read “…Influenza A target nucleic acid, wherein”;
There is a typographical error in claim 2(e)(i). An “or” is missing in the sentence, wherein the phrase should read “SEQ ID NO: 25 or an RNA”;
There is a grammatical error in claim 2(f). A conjunction should be added before moving into part (i) of the claim. It is recommended that the phrase read “…Influenza B target nucleic acid, wherein”;
There is a typographical error in claim 2(i). An “at” is missing at the beginning of the sentence wherein the phrase should read “at least one primer”;
There is a grammatical error in claim 2(n). The “comprises” at the beginning of the sentence should be removed as it was recited in the preamble of the claim;
In claim 63, the acronym “TCO” is recited, but not defined in the claim. An acronym should be defined the first time it appears in an independent claim or in the group of claims under an independent claim. For the purposes of examination, “TCO” is interpreted to mean “target capture oligonucleotides”, as defined in the specifications;
Claim 63 recites the limitation “one or more TCOs”. There is insufficient antecedent basis for this limitation in the claim as there is only one TCO recited in the claim. It is recommended that the phrase read “wherein the TCO is”;
There is a typographical error in claims 63 and 92. The phrase should read “n is an integer from 0 to 3 and m is an integer from 14 to 50” instead of “in an integer”;
There is a grammatical error in claim 69. A conjunction should be added before moving into part (i) of the claim. It is recommended that the phrase read “…Influenza B target nucleic acid, wherein”;
There is a typographical error in the preamble of claim 74. “[O]f” was deleted in the amended claim. The phrase should read “a target sequence of influenza B”;
There is a grammatical error in claim 74(a). There is a missing conjunction in the claim. It is recommended that the phrase read “contacting the sample with the first primer”;
There is a grammatical error in claim 86. The “a” should be removed as it is followed be a plural. It is recommended that the phrase read “comprising one or more probe oligonucleotides”;
There is a typographical error in the preamble of claim 89. There is a missing colon at the end of the sentence after “comprising”, wherein the phrase should read “composition or kit comprising:”;
There is a typographical error in claim 89. Two parts of the list are labeled with (e);
There is a grammatical error in claim 93(d). A conjunction should be added before moving into part (i) of the claim. It is recommended that the phrase read “…Influenza A target nucleic acid, wherein”;
There is a typographical error in claim 93(d)(ii). An “or” is missing in the sentence, wherein the phrase should read “SEQ ID NO: 18 or an RNA”;
There is a grammatical error in claim 93(e). A conjunction should be added before moving into part (i) of the claim. It is recommended that the phrase read “…Influenza A target nucleic acid, wherein”;
There is a typographical error in claim 93(e)(i). An “or” is missing in the sentence, wherein the phrase should read “SEQ ID NO: 25 or an RNA”;
There is a grammatical error in claim 93(f). A conjunction should be added before moving into part (i) of the claim. It is recommended that the phrase read “…Influenza B target nucleic acid, wherein”;
Appropriate correction is required.
Claim Rejections - 35 USC § 112
35 USC § 112(b)
10. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. — The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
11. Claims 1, 2, 12, 14, 15, 17, 26, 28, 40, 42 – 45, 63, 67, and 81 – 94 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.
12. Claims 1, 2, 12, 14, 15, 17, 26, 28, 40, 42 – 45, 63, 67, and 81 – 94 are vague and unclear, which renders the claims indefinite. These claims recite “composition or kit”. It is not clear if both limitations are essential for infringement or just one. The presence of multiple very different interpretations of the same claim language renders the claim indefinite. It is suggested that the claims be amended to read “composition or kit, each further…” to ensure both the composition and kit are encompassed by the claims, if it is intended that both are required to prevent infringement on the invention. However, an appropriate amendment is required.
13. Claim 17 recites different iterations of the limitation "the second, third, fourth, fifth, and sixth primer set" in parts (a) – (f) of the claim. There is insufficient antecedent basis for this limitation in the claim. There is no recitation of the second, third, fourth, fifth, and/or sixth primer set in claim 1, upon which claim 17 depends. These primer sets are recited in claim 2.
14. Claim 82 recites the limitation “the first primer set second primer” in part (a). There is insufficient antecedent basis for this limitation in the claim. There is no recitation of the first primer set in claim 81, upon which claim 82 depends. Additionally, the SEQ ID NOs drawn to the second primer set second primer in part (b); third primer set second primer in part (c); fourth primer set second primer in part (d); and fifth primer set in part (e) do not align with the SEQ ID NOs disclosed for the second, third, fourth, fifth, and sixth second primer set in parts (a)(ii), (b)(ii), (c)(ii), (d)(ii), and (e)(ii), respectively, in claim 81. Rather, the SEQ ID NOs set forth in part (a) of claim 82 align with those in part (a)(ii) of claim 81; part (b) with part (b)(ii); part (c) with part (c)(ii); part (d) with part (d)(ii); and part (e) with part (e)(ii). In the interest of compact prosecution, it will be inferred that part (a) of claim 82 is intended to be the second primer set second primer in part (a)(ii) of claim 81; part (b) the third primer set second primer in part (b)(ii) of claim 81; part (c) the fourth primer set second primer in part (c)(ii) of claim 81; part (d) the fifth primer set second primer in part (d)(ii) of claim 81; and part (e) the sixth primer set second primer in part (e)(ii) of claim 81. However, an appropriate amendment is required.
15. Claim 83 recites the limitation “the sixth primer set second primer” in part (e). There is insufficient antecedent basis for this limitation in the claim. There is no recitation of the sixth primer set in claim 82, upon which claim 83 depends. In the interest of compact prosecution, it will be inferred that part (e) of claim 82 is intended to be the sixth primer set, as discussed above in paragraph 14. However, an appropriate amendment is required.
16. Claim 85 recites the limitation “the second primer set” in part (a); “the third primer set” in part (b); “the fourth primer set” in part (c); “the fifth primer set” in part (d); “the sixth primer set” in part (e); and “the seventh primer set” in part (f). There is insufficient antecedent basis for this limitation in the claim. There is no recitation of the second, third, fourth, fifth, and/or sixth primer set in claim 15, which claim 85 is dependent upon.
17. Claim 87 is vague and unclear, which renders the claim indefinite. Part (e) and part (f) both recite “the influenza A region 2 probe”, but give different sequences. It is not clear if this is a typographical error or intentional. “[T]he influenza A region 2 probe” is recited in part (e) of claim 86, upon which claim 87 depends, whereas “the influenza B region 2 probe” is recited in part (f). In the interest of compact prosecution and in view of the instant specification, it will be inferred that this is a typographical error and claim 87(f) should be drawn to the influenza B region 2 probe. However, an appropriate amendment is required.
18. Claim 88 recites the limitation “the influenza B region 2 probe” in part (f). There is insufficient antecedent basis for this limitation in the claim. There is no recitation of the influenza B region 2 probe in claim 87, upon which claim 88 depends. In the interest of compact prosecution, it will be inferred that part (f) of claim 87 is intended to be the influenza B region 2 probe, as discussed above in paragraph 15. However, an appropriate amendment is required.
19. 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)
20. 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
21. Claims 1, 2, 12, 14, 15, 17, 26, 28, 40, 42 – 45, 63, 67, 69, 70, 72, 74, and 81 – 94 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre–AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre–AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
"The 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.
Claims 1, 2, 12, 14, 15, 17, 26, 28, 40, 42 – 45, 63, 67, 69, 70, 72, 74, and 81 – 94 are drawn to a composition or kit for determining the presence or absence of influenza B in a sample, wherein a region 1 primer set has a first primer that differs by no more than 0, 1, 2, 3, 4, or 5 nucleotides from the nucleotide sequence of SEQ ID NO: 91 and a second primer that differs by no more than 0, 1, 2, 3, 4, or 5 nucleotides from the nucleotide sequence of SEQ ID NOs: 86 or 87. Claims 2, 12, 14, 15, 17, 26, 28, 40, 42 – 45, 63, 67, 69, 70, 72, 74, and 81 – 94 add additional modifications to the composition or kit disclosed in claim 1. Claim 2 adds six more primer sets to the kit, for a grand total of seven primer sets, that are drawn to three regions of SARS-CoV-2, two regions of influenza A, and another region of influenza B, wherein the first and second primer in each set differs by no more than 0, 1, 2, 3, 4, or 5 nucleotides from the disclosed sequences. Similar iterations of “no more than 0, 1, 2, 3, 4, or 5” also occur in claims 12, 15, 28, 40, 45, 63, 69, 70, 81, 83, 86 – 88, and 92 – 94. Claim 26 discloses that the first primer set is to be capable of amplifying a target sequence through a transcription-mediated amplification reaction or a biphasic transcription-mediated amplification reaction.
SEQ ID NO: 91 is 20 nucleotides in length, SEQ ID NO: 86 is 21 nucleotides in length, and SEQ ID NO: 87 is 17 nucleotides in length. The claims encompass any sequence that differs by 0, 1, 2, 3, 4, and 5 nucleotides from SEQ ID NOs: 86, 87, or 91. A nucleotide sequence that differs by 5 nucleotides could have up to 5 substitutions, deletions, additions, or any combination thereof, along the length of SEQ ID NOs: 86, 87, or 91. This corresponds to a massive genus of 45 = 1024 possible combinations PER nucleotide sequence. Moreover, the nucleotide sequence of each differing sequence must align with the viral genome, wherein the amplification reaction can occur, which would be uncommon with such a large genus. This is also only considering the SEQ ID NOs disclosed in claim 1, i.e., the influenza B region 1 primers. The genus grows exponentially larger when expanded to the SEQ ID NOs disclosed for the other six primer sets. In general, this creates an enormous breadth of potential sequences that becomes innumerable when coupled with the massive genera of sequences per virus.
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 several genera that are comprised of innumerable sequences, yet, the specification has only adequately described, and successfully reduced to practice, those disclosed in Tables 1 – 8, 12, and 13 and examples 1 – 13. This includes SEQ ID NO: 72, which comprises SEQ ID NO: 91 (example 9, page 86). This is not representative of the extremely large genus of sequences claimed. One of ordinary skill in the art cannot conclude that Applicant was in possession of the innumerable sequences encompassed by the disclosed genera. Absent the disclosed sequences, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, each individual sequence utilized. Thus, it is clear that the breadth of the recited genera in the claims 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 tolerated mismatches in the primers that would still allow amplification of the target nucleic acid. 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., (The Effects of Internal Primer-Template Mismatches on RT-PCR: HIV-1 Model Studies, Nucleic Acids Research, (25)3, 654–658; Published 02/01/1997), 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 effect of primer-template mismatches on the detection and quantification of nucleic acids using the 5' nuclease assay. The Journal of molecular diagnostics: JMD, 12(1), 109–117; Published 01/2010), hereby Stadhouders, teaches that a single mismatch in the primer-template can have severe impacts on PCR amplification (page 109, left column). Green, S. J., et. al., (Deconstructing the Polymerase Chain Reaction: Understanding and Correcting Bias Associated with Primer Degeneracies and Primer Template Mismatches. PLoS ONE 10(5): e0128122; Published 05/21/2015), hereby Green, teaches that, ideally, the primers should match the target sequence, wherein a single mismatch results in poor amplification (page 2). Thus, when taken with the teachings of Christopherson, Stadhouders, and Green, 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.
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 “differing by no more than 0, 1, 2, 3, 4, or 5 nucleotides”.
35 USC § 112(d)
22. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS. — Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
23. Claims 81 – 85, 87, and 88 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 81 – 85, 87, and 88 recite “if present”, insinuating that the product may or may not be present in the composition or kit. Claim 2, which claims 81 – 85, 87, and 88 are dependent upon, recites require that the products be present. There are no additional limitations in claims 81 – 85, 87, and 88 that are not recited in claim 2 if the products are present in claims 81 – 85, 87, and 88. Thus, claims 81 – 85, 87, and 88. fail to further limit the subject matter of claim 2. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 101
24. 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.
25. Claims 1, 2, 12, 14, 15, 17, 26, 28, 40, 42 – 45, 63, 67, 69, 70, 72, 74, and 81 – 94 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 or an RNA equivalent or a DNA/RNA chimeric 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 1 recites “comprises a nucleotide sequence differing by no more than 0, 1, 2, 3, 4, or 5 nucleotides from the nucleotide sequence of SEQ ID NO: 91 or an RNA equivalent or a DNA/RNA chimeric 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 2, 12, 14, 15, 17, 26, 28, 40, 42 – 45, 63, 67, 69, 70, 72, 74, and 81 – 94. However, there are similar iterations of “or an RNA equivalent” occur in claims 2, 12, 15, 63, 69, 81 – 85, and 92 – 94 in relation to SARS-CoV-2 and influenza, which are both RNA viruses. Thus, RNA equivalents with the same sequence as the coding strand for either 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 1, 2, 12, 15, 63, 69, 81 – 85, and 92 – 94.
Claim Rejections - 35 USC § 103
26. 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.
27. Claims 1, 2, 12, 14, 15, 17, 26, 28, 40, 42 – 45, 67, 69, 70, 72, 74, 81 – 91, 93, and 94 are rejected under 35 U.S.C. 103 as being unpatentable over Hellyer, T., et. al. (US 20100273156 A1; Published 10/28/2010; Cited on page 2 of Applicant’s IDS on 09/29/2023 as U.S. Patent Document Cite No. 4), hereby Hellyer, in further view of Daunert, S., et. al., (US 10689716 B1; Published 06/23/2020; Cited in Applicant’s IDS on 07/31/2025 as U.S. Patent Document Cite No. 001), hereby Daunert, and Buck, G. A., et. al., (Design strategies and performance of custom DNA sequencing primers. BioTechniques, 27(3), 528–536; Published 09/1999), hereby Buck.
Hellyer teaches methods, including a kit, to detect the absence or presence of influenza in a sample using nucleic acids primers and probes derived from influenza A and influenza B viruses (page 1, paragraph 0001; page 2, paragraphs 0009 and 0013), as required in instant claims 1, 2, and 69. It is further taught that there are two primers, (1) the signal primer that is complementary to the target sequence and (2) the amplification primer, that are designed to hybridize regions of the influenza A and influenza B genomes that are unique to each strain (page 2, paragraph 0011), as disclosed in instant claims 1, 2, and 69. The primers are approximately 10 – 75 nucleotides in length, but preferably 15 – 50 nucleotides in length (page 7, paragraphs 0050 and 0051). Page 4, paragraph 0024 and page 7, paragraph 0054 teach that the primers can be a modified nucleotide that is optionally linked to specialized sequence required for the amplification reaction or to facilitation detection, i.e., a probe, as defined in instant claims 28, 40, and 67. It is further taught that the probe may be a detectable moiety, including donor-quencher dye pairs, fluorophores, and radioactive labels, or a molecular beacon that hybridizes to itself (page 3, paragraph 0017; page 5, paragraphs 0035 – 0037; claim 4), as disclosed in instant claims 42 – 44. The amplification primer may also have an RNA polymerase promoter near the 5’ end (page 7, paragraph 0050), as recited in instant claim 14. These primers may be used in various nucleic acid amplification techniques, including transcription mediated amplification (TMA; page 2, paragraph 0012; page 6, paragraph 0042; claim 24), as disclosed in instant claim 26. During these reactions, the signal primer binds to the sequence downstream from the amplification primer and each primer is simultaneously extended, wherein a signal is only detected when there is sufficient amplification of the target sequence due to the properties of the detectable moiety (page 5, paragraphs 0030 – 0032; page 8, paragraphs 0056 and 0059; figure 1), as required in instant claims 1, 69, 70, and 74. This reaction takes place in a mixture, i.e., a solution, wherein there are primers present for both influenza A and B in a single multiplex reaction (page 1, paragraph 0005; page 6, paragraphs 0043, 0044, and 0046), as defined in instant claims 2, 17, 72, 81 – 91, 93, and 94. It is further taught that one or more of the primers, i.e., multiple primers, directed to either influenza A, influenza B, or both strains may be in the reaction mixture to allow for specific detection of either strain with minimal false positive results (page 2, paragraph 0013). Thus, "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). See also In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992); and In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023).
While Hellyer does not teach methods for detecting SARS-CoV-2, influenza A, and influenza B in a single sample, as recited in instant claims 2, 17, 81 – 91, 93, and 94, it does teach that detection of influenza A and B may be conducted in a reaction mixture which also contains primers and probes for the detection of other viral respiratory analytes, including coronaviruses (page 6, paragraph 0046). Daunert teaches methods and test kits with primer pairs for detecting the presence of coronavirus polynucleotides in a sample, wherein the coronavirus polynucleotide may be from SARS-CoV-2 (abstract; column 1, lines 19 – 32; column 4, lines 29 – 42), as defined in instant claims 2, 17, 81 – 91, 93, and 94.
Nonetheless, neither Hellyer nor Daunert explicitly teach all of the primers disclosed in the instant claims. Hellyer does teach that the target-binding sequence for influenza B corresponds to the influenza B matrix gene, denoted as SEQ ID NO: 26, which has 100% sequence similarity to the elected instant SEQ ID NOs: 72 and 106, as reproduced below on the left and right, respectively. Moreover, Buck provides evidence for the equivalence of primers. Buck teaches 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). Like Hellyer, 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 influenza B matrix gene is known in the art, as taught by Hellyer and required by instant claims 1, 2, 12, 15, 28, 40, 45, 69, 70, 81 – 91, 93, and 94. Hellyer also teaches the target sequence of the influenza A matrix gene, denoted as SEQ ID NO: 25, as disclosed in instant claims 2, 17, 81 – 91, 93, and 94. For
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example, a sequence alignment revealed 100% sequence similarity between SEQ ID NO: 25 and instant SEQ ID NO: 1,
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as reproduced below, both of which are drawn to influenza A. Moreover, Daunert teaches the SARS-CoV-2 genome, as disclosed by SEQ ID NO: 12. Since all of the target genomes are known in the art, it would have been obvious to a person having ordinary skill in the art to design primers that have variable lengths with a reasonable expectation of success.
Hellyer, Daunert, and Buck 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 for the SARS-CoV-2 genome disclosed in Daunert and combine those with modifications and influenza genomes taught by Hellyer. This obviousness is mainly owed to Hellyer and Daunert teaching methods/kits for detecting respiratory viruses 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 Hellyer, Daunert, and Buck before the effective filing date of the claimed invention with a reasonable expectation of success to provide a more rapid and sensitive means of specifically detecting influenza and SARS-CoV-2 in a sample (Hellyer, page 1, paragraph 0004; Daunert, column 1, lines 33 – 40). 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 methods of detecting SARS-CoV-2, influenza A, and influenza B into a single kit to detect as many possible sources of symptoms at once, i.e., determine the causative virus, as quickly as possible. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415–421, 82 USPQ2d 1385, 1395–97 (2007) and MPEP §§ 2143(G) and 2143.02.
28. Claims 63 and 92 are rejected under 35 U.S.C. 103 as being unpatentable over Hellyer, Daunert, and Buck as applied to claims 1, 2, 12, 14, 15, 17, 26, 28, 40, 42 – 45, 67, 69, 70, 72, 74, 81 – 91, 93, and 94 above, and further in view of Thermo Fisher Scientific – Poly(A) Tailing Kit Tech Notes (Accessed 09/22/2019), hereby Thermo.
29. Hellyer, Daunert, and Buck make obvious claims 1 and 2, but do not teach the addition of a poly(A) sequence to the primers, as required in instant claims 63 and 92. However, Thermo teaches that polyadenylation plays an important role in the stabilization of RNA and enhances the efficiency of translation initiation (first paragraph).
Hellyer, Daunert, Buck, and Thermo 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 add the polyadenylation as disclosed by Thermo with the designed primers as taught by Buck for the SARS-CoV-2 genome disclosed in Daunert and combine those with the modifications and influenza genomes taught by Hellyer. This obviousness is mainly owed to Hellyer and Daunert teaching methods/kits for detecting respiratory viruses in a sample using primers wherein Buck and Thermo teach primer optimization and stability. Therefore, it would have been obvious to a person having ordinary skill in the art to have combined the teachings of Hellyer, Daunert, Buck and Thermo before the effective filing date of the claimed invention with a reasonable expectation of success to improve translation initiation (first 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 methods of detecting SARS-CoV-2, influenza A, and influenza B into a single kit to detect as many possible sources of symptoms at once, i.e., determine the causative virus, as quickly as possible, with optimal stability. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415–421, 82 USPQ2d 1385, 1395–97 (2007) and MPEP §§ 2143(G) and 2143.02.
Conclusion
30. Claims 1, 2, 12, 14, 15, 17, 26, 28, 40, 42 – 45, 63, 67, 69, 70, 72, 74, and 81 – 94 are rejected. No claims are allowed.
31. 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