DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-15 and 29-31, in the reply filed on 06/30/2026 is acknowledged.
Claims 18-23 and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Amendments to claim 4 are acknowledged.
Claims 16-17, 24-25, and 27-28 are canceled.
Claims 1-15, 18-23, 26, and 29-31 are pending.
Claims 1-15 and 29-31 are under examination on the merits.
Priority
This application 18/583,105 filed on 02/21/2024 claims the benefit of provisional U.S. Patent Application No. 63/447,815, filed on 02/23/2023.
The priority date of claim 1 and its dependent claims is determined to be 02/23/2023, the filing date of provisional U.S. Patent Application No. 63/447,815.
Specification
The disclosure is objected to because of the following informalities: The specification recites “destabilizing dNTP: canconical dNTP” (p. 3, para 19). This appears to be a typo intended to be “canonical dNTP”. Appropriate correction is required.
The use of terms which are trade names or marks used in commerce (including EvaGreen® , has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM, 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.
Claim Interpretation
Claims 1, 4, 6-9, 13 and 15 include the term “optionally” to describe structure limitations. Claim scope is not limited by claim language that makes optional but does not require specific structural features. MPEP 2111.04.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-15 and 29-31 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation “wherein each primer comprises no more than four, three, two, or one canonical bases that hybridize to the base corresponding to the destabilizing dNTP”. As written, the limitation reads on the primers of the primer pair and requires a primer with typical A,C,T,or G bases. It is unclear whether the limitation requires a limit on the number of types of canonical base (i.e. A, C, T, or G) or a limit on the number of individual bases in the primer (i.e. no more than 4 A’s).
Further, the phrase “canonical bases that hybridize to the base corresponding to the destabilizing dNTP” is unclear. As written, it is unclear what the canonical bases of the primer are intended to hybridize to. For example, if the “destabilizing dNTP” is dITP it is unclear if the “base corresponding to the destabilizing dNTP” is G (which dITP is a substitute for) or C (the base corresponding to, i.e. pairing with, dITP). It is noted that, in the case of pairing to the destabilizing dNTP, A and T can also hybridize to dITP.
For purposes of examination claim 1 is interpreted to require a primer that comprises no more than 4 individual nucleotides of a canonical base that is replaced by, rather than pairs with, the destabilizing dNTP.
Claims 2-15 and 29-31 are similarly indefinite because they directly or indirectly depend from claim 1.
Claim 7 recites the limitation “incorporation of the at least one destabilizing base”. There is insufficient antecedent basis for this limitation in the claim. Claim 1, which claim 7 depends from, recites “at least one destabilizing dNTP”.
Claim 9 recites the limitation “wherein the primer pair defines an amplicon that has a length of about 50 bases to about 100 bases, optionally about 65 bases to about 85 bases”. The claim is indefinite because it encompasses embodiments both including and excluding lengths from the broader range. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, the claim recites the broad recitation “a length of about 50 bases to about 100 bases”, and the claim also recites “optionally about 65 bases to about 85 bases”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 11 recites the limitation “wherein the probe comprises no more than six, five, four, three, or 2 canonical bases that hybridize to the base corresponding to the destabilizing dNTP”. As written, the limitation reads on the primers of the primer pair and requires a primer with typical A,C,T,or G bases. It is further unclear whether the limitation requires a limit on the number of types of canonical base (i.e. A, C, T, or G) or a limit on the number of individual bases in the primer (i.e. no more than 4 A’s).
Further, the phrase “canonical bases that hybridize to the base corresponding to the destabilizing dNTP” is unclear. As written, it is unclear what the canonical bases of the primer are intended to hybridize to. For example, if the “destabilizing dNTP” is dITP it is unclear if the “base corresponding to the destabilizing dNTP” is G (which dITP is a substitute for) or C (the base corresponding to, i.e. pairing with, dITP). It is noted that, in the case of pairing to the destabilizing dNTP, A and T can also hybridize to dITP. It is further unclear if the bases being hybridized to are required to be in the target nucleic acid.
For purposes of examination claim 11 is interpreted to require a primer that comprises no more than 6 individual nucleotides of a canonical base that is replaced by, rather than pairs with, the destabilizing dNTP.
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.
Claims 1-15 and 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Chu et al. (WO2020221915).
Regarding claim 1, Chu teaches kits a methods for nucleic acid amplification. Chu teaches a kit comprising dITP (a destabilizing dNTP) and primers (p. 3, lines 7-8). The primer pair (SEQ ID NOs 1 and 2) further comprise a modified base, C-5 propynyl-dU (p. 11, lines 33-34 and Table 1), which reads on each primer in a primer pair comprising a modification to increase the stability of a duplex.
Chu further teaches a primer pair (SEQ ID NOs 1 and 2) comprising A, C, and T bases, which read on canonical bases that hybridize to a base corresponding to dITP (Table 1).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Chu to arrive at the instantly claimed invention. The modification would have entailed limiting the number of C bases in the primer to fewer than four. Determining an appropriate primer content is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. Primer design was well-known and conventional to one of skill in the art at the time of filing. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claims 2 and 14, Chu teaches a primer pair (SEQ ID NOs 1 and 2) with the modified base C-5 propynyl-dU (Table 1).
Regarding claim 3, Chu does not teach the primer modification i comprises one or more peptide nucleic acid, one or more locked nucleic acid, and one or more minor groove binder.
However, Chu teaches other modified nucleotides known in the art can be substituted in the oligonucleotides (primers) (p. 12, lines 4-5).
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Chu to arrive at the instantly claimed invention. The modification would have entailed selecting an alternative modification of the primers of the primer pair. Determining an appropriate primer modification is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. Primer design was well-known and conventional to one of skill in the art at the time of filing and, further, Chu teaches the kit encompasses other modifications known in the art at the time of filing. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 4, Chu teaches a master mix comprising dNTPS (p. 24, lines 16-17). Chu further teaches a ratio of dITP:dGTP of 3:1 (p. 5, line 25).
Regarding claim 5, Chu teaches an embodiment with no dGTP (the canonical dNTP corresponding to the destabilizing dNTP) (Table 3).
Regarding claim 6, Chu teaches a primer pair (SEQ ID NOs 1 and 2) with a Tms of 63.3 and 68.3 respectively (Table 1).
Regarding claim 7, Chu teaches an amplicon with the incorporation of at least one modified base with a Tm of 74.1 degrees C (p. 25, lines 8-9).
Regarding claim 8, Chu teaches an amplicon with a GC content of 51% and does not teach an amplicon with a GC content of less than 50%.
However, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Chu to arrive at the instantly claimed invention. The modification would have entailed limiting the GC content of the amplicon to less than 50%. Determining an appropriate GC content is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 9, Chu teaches an amplicon (SEQ ID NO. 4) that has a length of 113 bases, which reads on a length of about 100 bases.
Regarding claim 10, Chu teaches a kit comprising a probe (p. 3, lines 7-8).
Regarding claim 11, Chu teaches a probe (SEQ ID NO. 3, Table 1) comprising seven canonical C bases (bases that hybridize to the base corresponding to the destabilizing dNTP, when the base corresponding to the destabilizing dNTP is G) and does not teach the primer comprises no more than six.
However, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Chu to arrive at the instantly claimed invention. The modification would have entailed limiting the number of C bases in the probe to fewer than six. Determining an appropriate probe content is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan. Chu compares probe design to primer design (p.12, lines 22-23) and primer design was well-known and conventional to one of skill in the art at the time of filing. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Regarding claim 12, Chu teaches the probe (SEQ ID NO. 3, Table 1) comprises C-5-propynyl-dU, which reads on at least one stabilizing base.
Regarding claim 13, Chu teaches each primer of the primer pair of SEQ ID Nos: 1 and 2 comprise five (SEQ ID no: 1) or two C-5-propynyl-dU bases (Table 1).
Regarding claim 15, Chu teaches the probe SEQ ID NO: 5 has a Tm of 78.6 (Table 1), which reads on a Tm of about 80 degrees C.
Regarding claim 29, Chu teaches the kit comprises dITP (p. 3, lines 7-8).
Regarding claim 30, Chu teaches reagents include DMSO (p. 14, line 8), a PCR enhancer.
Regarding claim 31, Chu teaches a method directed to amplification of RNA (p. 3, lines 4-5) and further teaches a reverse transcription step (p. 27, line 4). Chu teaches the kit comprises reagents for performing the method (p.3, lines 7-8), including enzymes (p. 21, lines10-12) but does not explicitly teach the kit comprises a reverse transcriptase.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the teachings of Chu to arrive at the instantly claimed invention. The modification would have entailed including a reverse transcriptase reagent in the kit. One would have been motivated to include a revers transcriptase in order to accomplish the stated goal of providing a kit comprising the necessary regent for performing RNA amplification including the reverse transcription step taught by Chu. There would have been a reasonable expectation of success given the underlying materials and methods are widely known, successfully demonstrated, and commonly used as evidenced by the prior art.
Conclusion
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/JESSICA GRAY/Examiner, Art Unit 1682
/WU CHENG W SHEN/Supervisory Patent Examiner, Art Unit 1682
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