DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status and Formal Matters
This action is in response to papers filed 12/22/2025.
Claims 1, 3, 6, 10, 12, 14-15, 38 have been amended.
Claims 1, 3, 6, 10, 12, 14-15,20, 27, 38, 41, 46, 53-55, 61, 64-66 are pending.
Applicant’s election without traverse of Group I, virus, and two nucleic acid molecules in the reply filed on 7/15/2025 is acknowledged.
Claims 20, 27, 41-, 46, 53-55, 61, 64-66 withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected inventions/species , there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 7/15/2025.
Claims 1, 3, 6, 10, 12, 14-15, and 38 are being examined.
The objection to the drawings has been withdrawn in view of the replacement sheets.
The sequences compliance issue has been withdrawn in view of the amendment to the specification.
Priority
The instant application was filed 12/06/2021 and is a national stage entry of PCT/IB2020/055348 with an international filing date: 06/07/2020 and claims priority from provisional application 62858874 , filed 06/07/2019.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Rejections - 35 USC § 112
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 10 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 10 recites, “degenerate sequence.” The specification teaches, “a primer
has a "degenerate" sequence i.e., the nucleic acid sequence is a composition of sequences that have different nucleotides at the same position such that the primer is a
mixture of different sequences that can hybridize to multiple, different target nucleic acids. In other words, a degenerate sequence can be complementary to a plurality of
target nucleic acid sequences.” Thus as the claim requires a single sequence it is unclear what is required of degenerate. It is unclear if degenerate requires a consensus
sequence present in multiple species, a population of nucleic acids, or something else.
Response to Arguments
All the 112(b) rejections excepts those of claim 10 are withdrawn in view of the amendments.
The response traverses the rejection asserting, “The Applicant respectfully submits that degenerate sequences are well known in the art and that a person of ordinary skill would recognize that such a sequence refers to an indeterminate sequence.." This argument has been thoroughly reviewed but is not considered persuasive as it is inconsistent with the teachings of the specification.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 3, 6, 10, 12, 14-15, and 38 is/are rejected under 35 U.S.C. 102(a)(1)/ 102 (a)(2) as being anticipated by Ryckelynk (WO2018/198013).
The specification in (0150 states, “:An "aptamer," as used herein, refers to a nucleic acid molecule that can bind a ligand.” Thus this recitation is broad.
Further the claims require a 3’end and a 5’ end. The broadest reasonable interpretation of 5’ end is any portion which has a sequence 3’ of it. The broadest reasonable interpretation of 3’ end is any portion of a nucleic acid sequence which has nucleotides 3’ of it.
With regards to claim 1, 14, Ryckelynk teaches fluorogenic aptamer encoding template sequences for the amplification of nucleic acids using rolling circle amplification (figure 33-34 and 52).
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Thus Ryckelynk teaches a nucleic acid molecule encoding a nucleic acid which comprises a nucleic acid which is can of hybridize to a target sequence and encodes a Mango aptamer and a 5’ end which can hybridize to a portion of nucleic acid sequence and 3 terminal nucleotides do not bind to the first sequence.
With regards to claim 3, Ryckelynk teaches the sequences of Figure 52 which are between about 20 and 100 nucleotides in length.
Claim 6 recites, “wherein at least the terminal nucleotide of the 5' end of the second nucleic acid sequence is complementary to at least the terminal nucleotide of the 5' end of the first nucleic acid to form at least a portion of [[the]]a terminal stem structure.” This is a little confusing as claim 1 requires the first nucleic sequence and second nucleic acid sequence together form the first nucleic acid molecule. The claim and specification fail to provide any definition to define where the first nucleic acid sequence begins or ends and the second nucleic acid sequence begins or ends.
With regards to claim 6, Ryckelynk teaches the hairpin loops and thus the 5’ end of the second nucleic acid sequence is complementary to the 5’ end of the first nucleic acid sequence. (figure 34).
The specification teaches, “00158] In some embodiments, a primer has a "degenerate" sequence i.e., the nucleic acid sequence is a composition of sequences that have different nucleotides at the same position such that the primer is a mixture of different sequences that can hybridize to multiple, different target nucleic acids. In other words, a degenerate sequence can be complementary to a plurality of target nucleic acid sequences.”
With regards to claim 10. Ryckelynk teaches the sequences human and mouse beta actin and thus degenerate sequences in view of teachings of the specification with respect to degenerate. (figure 52).
With regards to claim 12, Ryckelynk teaches the target is synthetic or animal human and mouse beta actin a (figure 52)
With regards to claim 15, Ryckelynk teaches t7 promoter (page 28).
Although claim 38 recites the term “kit”, the claim contains no structural requirements to distinguish it from a composition, nor is the term defined to be so limited in the specification. Accordingly, the claim has been given the reasonable interpretation to encompass a composition containing the claimed molecule.
MPEP 2112.01 III states:
The court has extended the rationale in the printed matter cases, in which, for example, written instructions are added to a known product, to method claims in which "an instruction limitation" (i.e., a limitation “informing” someone about the existence of an inherent property of that method) is added to a method known in the art. King Pharmaceuticals, Inc. v. Eon Labs, Inc., 616 F.3d 1267, 1279, 95 USPQ2d 1833, 1842 (2010). Similar to the inquiry for products with printed matter thereon, for such method cases the relevant inquiry is whether a new and unobvious functional relationship with the known method exists. In King Pharma, the court found that the relevant determination is whether the "instruction limitation" has a "new and unobvious functional relationship" with the known method of administering the drug with food. Id.. The court held that the relationship was non-functional because "[I]forming a patient about the benefits of a drug in no way transforms the process of taking the drug with food." Id. That is, the actual method of taking a drug with food is the same regardless of whether the patient is informed of the benefits. Id. “In other words, the ‘informing’ limitation ‘in no way depends on the method, and the method does not depend on the ‘informing’ limitation.’" Id. (citing In re Ngai, 367 F.3d 1336, 1339 (Fed. Cir. 2004)); see also In re Kao, 639 F.3d 1057, 1072-73, 98 USPQ2d 1799, 1811-12 (Fed. Cir. 2011).
With regards to claim 38, Ryckelynk teaches the composition and thus anticipates the claims.
Response to Arguments
The response traverses the rejection asserting, “The Applicant respectfully submits that Ryckelynk does not disclose nucleic acid molecules configured as claimed, for example, where the aptamer-encoding template sequence is positioned at the 3' end of the first nucleic acid sequence, the 5' end of the second nucleic acid sequence is covalently attached to the 3' end of the first nucleic acid sequence, and wherein the 3' end of the second nucleic acid sequence does not substantially hybridize to the first nucleic acid sequence.” This argument has been thoroughly reviewed but is not considered persuasive as the 5’end merely requires there is something 3’ to it and the 3’end requires there is something 5’ to it. Further figure 52 provides
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Thus Ryckelynk teaches a nucleic acid molecule encoding a nucleic acid which comprises a nucleic acid which is can of hybridize to a target sequence and encodes a Mango aptamer and a 5’ end which can hybridize to a portion of nucleic acid sequence and 3 terminal nucleotides do not bind to the first sequence.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1, 3, 6, 10, 12, 14-15, and 38 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ryckelynk (WO2018/198013), Voloshin (ACS Chem. Biol. 2014, 9, 2412−2420), Burch (Virus Research Volume 228, 15 January 2017, Pages 141-146)
The specification in (0150 states, “:An "aptamer," as used herein, refers to a nucleic acid molecule that can bind a ligand.” Thus this recitation is broad.
Further the claims require a 3’end and a 5’ end. The broadest reasonable interpretation of 5’ end is any portion which has a sequence 3’ of it. The broadest reasonable interpretation of 3’ end is any portion of a nucleic acid sequence which has nucleotides 3’ of it.
With regards to claim 1, 14, Ryckelynk teaches fluorogenic aptamer encoding template sequences for the amplification of nucleic acids using rolling circle amplification (figure 33-34 and 52).
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Thus Ryckelynk teaches a nucleic acid molecule encoding a nucleic acid which comprises a nucleic acid which is can of hybridize to a target sequence and encodes a Mango aptamer and a 5’ end which can hybridize to a portion of nucleic acid sequence and 3 terminal nucleotides do not bind to the first sequence.
Ryckelynk does not specifically teach the target nucleic acid is a virus.
Dolgosheina teaches, “In an ideal RNA tracking system, KD should be minimized, as only then will low concentrations of RNA be fully complexed with fluorophore, while E should be maximized, so that the signal-to-noise ratio of the system is as high as possible. Systems, such as the GFP-MS28 and the recent Spinach aptamer,1,9,10 optimize one or the other of these two constraints but fail to simultaneously optimize both (Table 1). The MS2 system fuses a fluorescent protein reporter to a peptide sequence recognized by an RNA motif with nanomolar affinity and has proven successful in RNA live cell imaging.11−18 Yet, it suffers since the intrinsic fluorescence of the unbound protein reporter is not enhanced upon binding to the target RNA (i.e., FE = n, where n is the number of encoded MS2 RNA sequence elements), making it potentially difficult to discern the signal coming from the free fluorophore itself or the fluorophore bound to RNA. Conversely, despite the high fluorescent enhancement of the Spinach aptamer (FE = 2,000), the system has a poor KD. 9 This places the fluorescent efficiency of the Spinach aptamer some six times lower than that of the toxic malachite green aptamer (Table 1), which has both a higher FE and lower KD. (2412, 1st column-2nd column) Dolgosheina teaches detection of C. elegans sequences and synthetic bacterial sequences.
Burch teaches detection of viral DNA with spinach aptamer (title throughout).
Therefore it would have been prima facie obvious to one of ordinary skill in the art prior to the effective fling date of the claims to target viral nucleic acids with the mango aptamer taught by Ryckelynk and Dolgosheina. The artisan would be motivated to use mango aptamer taught by Ryckelynk and Dolgosheina to examine it is as sensitive of more sensitive than the spinach aptamer of Burch. The artisan would have a reasonable expectation of success as the artisan is merely substituting one molecular biology construct for another.
With regards to claim 3, Ryckelynk teaches the sequences of Figure 52 which are between about 20 and 100 nucleotides in length.
Claim 6 recites, “wherein at least the terminal nucleotide of the 5' end of the second nucleic acid sequence is complementary to at least the terminal nucleotide of the 5' end of the first nucleic acid to form at least a portion of [[the]]a terminal stem structure.” This is a little confusing as claim 1 requires the first nucleic sequence and second nucleic acid sequence together form the first nucleic acid molecule. The claim and specification fail to provide any definition to define where the first nucleic acid sequence begins or ends and the second nucleic acid sequence begins or ends.
With regards to claim 6, Ryckelynk teaches the production of hairpin loops and thus the 5’ end of the second nucleotide is complementary to the 5’ end of the first nucleotide. (figure 34).
The specification teaches, “00158] In some embodiments, a primer has a "degenerate" sequence i.e., the nucleic acid sequence is a composition of sequences that have different nucleotides at the same position such that the primer is a mixture of different sequences that can hybridize to multiple, different target nucleic acids. In other words, a degenerate sequence can be complementary to a plurality of target nucleic acid sequences.”
With regards to claim 10. Ryckelynk teaches the sequences human and mouse beta actin and thus degenerate sequences in view of teachings of the specification with respect to degenerate. (figure 52).
With regards to claim 12, Ryckelynk teaches the target is synthetic or animal human and mouse beta actin a (figure 52)
With regards to claim 15, Ryckelynk teaches t7 promoter (page 28).
Although claim 38 recites the term “kit”, the claim contains no structural requirements to distinguish it from a composition, nor is the term defined to be so limited in the specification. Accordingly, the claim has been given the reasonable interpretation to encompass a composition containing the claimed molecule.
MPEP 2112.01 III states:
The court has extended the rationale in the printed matter cases, in which, for example, written instructions are added to a known product, to method claims in which "an instruction limitation" (i.e., a limitation “informing” someone about the existence of an inherent property of that method) is added to a method known in the art. King Pharmaceuticals, Inc. v. Eon Labs, Inc., 616 F.3d 1267, 1279, 95 USPQ2d 1833, 1842 (2010). Similar to the inquiry for products with printed matter thereon, for such method cases the relevant inquiry is whether a new and unobvious functional relationship with the known method exists. In King Pharma, the court found that the relevant determination is whether the "instruction limitation" has a "new and unobvious functional relationship" with the known method of administering the drug with food. Id.. The court held that the relationship was non-functional because "[i]nforming a patient about the benefits of a drug in no way transforms the process of taking the drug with food." Id. That is, the actual method of taking a drug with food is the same regardless of whether the patient is informed of the benefits. Id. “In other words, the ‘informing’ limitation ‘in no way depends on the method, and the method does not depend on the ‘informing’ limitation.’" Id. (citing In re Ngai, 367 F.3d 1336, 1339 (Fed. Cir. 2004)); see also In re Kao, 639 F.3d 1057, 1072-73, 98 USPQ2d 1799, 1811-12 (Fed. Cir. 2011).
With regards to claim 38, Ryckelynk teaches the composition and thus anticipates the claims.
Response to Arguments
The response traverses the rejection asserting, “The Applicant respectfully submits that Ryckelynk does not disclose nucleic acid molecules configured as claimed, for example, where the aptamer-encoding template sequence is positioned at the 3' end of the first nucleic acid sequence, the 5' end of the second nucleic acid sequence is covalently attached to the 3' end of the first nucleic acid sequence, and wherein the 3' end of the second nucleic acid sequence does not substantially hybridize to the first nucleic acid sequence.” This argument has been thoroughly reviewed but is not considered persuasive as the 5’end merely requires there is something 3’ to it and the 3’end requires there is something 5’ to it. Further figure 52 provides
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Thus Ryckelynk teaches a nucleic acid molecule encoding a nucleic acid which comprises a nucleic acid which is can of hybridize to a target sequence and encodes a Mango aptamer and a 5’ end which can hybridize to a portion of nucleic acid sequence and 3 terminal nucleotides do not bind to the first sequence.
Summary
No claims are allowed.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to STEVEN C POHNERT PhD whose telephone number is (571)272-3803. The examiner can normally be reached Monday- Friday about 6:00 AM-5:00 PM, every second Friday off.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571)272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Steven Pohnert/Primary Examiner, Art Unit 1683
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