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 .
Status of the Claims
Claims 1-3, 5-6, 8-9, 11-12, 15-16, 18, 20-21, 25, 28, 30-32, and 41 are pending. Claims 1-3, 5-6, 8-9, 11-12, 15-16, and 18 are the subject of this NON-FINAL Office Action. Claims 20-21, 25, 28, 30-32, and 41 have been withdrawn. This is the first action on the merits.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-3, 5-6, 8-9, 11-12, and 18, in the reply filed on 12/19/2025 is acknowledged. After further consideration, Group II, claims 15-16, will be rejoined and examined with Group I. Claims 20-21, 25, 28, 30-32, and 41 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
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;
ii) the date of creation; and
iii) 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 - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located in Fig. 6 and Fig. 7. Every sequence in Fig. 6 and in Fig. 7 must have an entry in the sequence listing. The reversed sequences (HRR_0764_R (reversed) in Fig. 6, ADHv3_0323-R in Fig. 7, and ADHv3_0245-F in Fig. 7) must have their own entries in the sequence listing.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, 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;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. The sequences are located in Fig. 6 and Fig. 7.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
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 incorporation-by-reference paragraph, 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
Claim 5 and 18 are objected to because of the following informalities:
Line 2 of claim 5 recites “the at least chimeric primer.” The phrase should be corrected to “the at least one chimeric primer.”
Claim 18 refers to “the chimeric primer.” The phrase should be corrected to “the at least one chimeric primer.”
Appropriate correction is required.
Claim Interpretation
Claim 1 recites a method for generating chimeric primers capable of amplifying at least a portion of a template DNA molecule, while minimizing or eliminating the formation of primer dimers. The claim does not require the generation of these chimeric primers.
The limitation “while minimizing or eliminating the formation of primer dimers” is interpreted as functional language. The claim will be interpreted as encompassing all chimeric primers which fulfill the recited structure of an oligonucleotide comprising DNA and RNA bases and has a sequence identical to that of one of the identified DNA primers except for a first segment wherein at least two adjacent DNA bases are replaced by corresponding RNA bases.
The claim encompasses embodiments wherein the two adjacent DNA bases replaced by corresponding RNA bases can be located anywhere within the chimeric primer.
The claim recites steps of selecting a sequence for at least one chimeric primer. The claim does not provide further limitations on how the sequence is selected. The claim will be interpreted as encompassing any method of selecting a sequence.
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 1-3, 5-6, 8-9, 11-12, 15-16, and 18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. The claim(s) recite(s) the steps of identifying a primer dimer produced during a PCR assay, identifying one or more DNA primers that produce the primer dimer, identifying an overlapping region produced when the one or more DNA primers hybridize during the PCR assay, and selecting a sequence for at least one chimeric primer. These steps are recited at a high level of generality and are therefore mental processes which can be performed in the human mind. The claims only require the steps of “identifying” and “selecting,” and do not provide additional limitations on how these steps are to be performed. The “generating” step of the claim is optional; thus, the claim only requires mental processes which can be performed in the human mind.
This judicial exception is not integrated into a practical application because the claims do not recite additional elements. Claim 1 does not require the generation of the chimeric primer, and the dependent claims recite additional mental processes which can be performed in the human mind or additional limitations on the sequence of the chimeric primer which is not required to be generated. Claim 15 does not recite a generation step and does not recite additional elements.
The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because they do not add significantly more to the exception. Claim 1 does not recite additional limitations. The dependent claims recite additional mental processes which can be performed in the human mind (e.g. claim 8 recites “selecting a sequence” at a high level of generality), or recite additional limitations on the sequence of the chimeric primer which is not required to be generated according to claim 1.
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.
Claim1-3, 5-6, 8-9, 11-12, 15-16, and 18 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 a method for generating chimeric primers capable of amplifying at least a portion of a template DNA molecule, while minimizing or eliminating the formation of primer dimers. It is unclear from claim 1 how the chimeric primers minimize or eliminate the formation of primer dimers.
Firstly, the claims do not require that the chimeric primer be generated. The chimeric primer is only required to have a sequence identical to one of the identified DNA primers except for a first segment wherein at least two adjacent DNA bases are replaced by corresponding RNA bases. These adjacent bases can be located anywhere within the chimeric primer. It is unclear whether any adjacent DNA bases replaced by corresponding RNA bases minimize or eliminate the formation of primer dimers, or whether these bases must be located in a particular region of the chimeric primer.
The claim recites identifying an overlapping region produced when the one or more DNA primers hybridize during the PCR assay. It is unclear how this step relates to the generation of the chimeric primers. Claim 1 does not require this overlapping region to be used in the sequence selection of the chimeric primers. While the dependent claims use the overlapping region as a reference point for where the replaced adjacent bases should be located, it is not clear from claim 1 whether these locations are a requirement for the chimeric primers to perform as recited, or whether the replaced bases can be located anywhere in the chimeric primer.
Similarly, claim 15 only recites identifying a non-specific amplification fragment, identifying one or more DNA primers that produce the non-specific amplification fragment, and selecting a sequence for at least one chimeric primer. It is unclear how these steps will result in minimizing or eliminating non-specific amplification, whether any two adjacent DNA bases can be replaced, or whether specific bases should be replaced.
Claims 2-3, 5-6, 8-9, 11-12, 16, and 18 are rejected by virtue of their dependencies upon claims 1 and 15.
Allowable Subject Matter
The claims are free of the prior art. The prior art does not teach or suggest generating a chimeric primer wherein the chimeric primer is identical to an existing DNA primer except for a first segment wherein at least two adjacent DNA bases are replaced by corresponding RNA bases.
Kurn et al. (US 2009/0203085 A1; previously cited) teaches a chimeric primer comprising a DNA segment and an RNA segment (par. 0182), but does not teach or suggest replacing at least two adjacent DNA bases by corresponding RNA bases.
Peleg (WO 2009/004630 A1, cited on the IDS filed 06/29/2022) teaches primers with non-adjacent RNA bases (Abstract). Peleg specifically teaches that the RNA bases are not adjacent to each other. Peleg does not teach or suggest adjacent RNA bases in the primers.
Goering (US 2009/0253129 A1) teaches replacing DNA bases with LNA bases, but does not teach or suggest the LNA bases being adjacent to one another (Fig. 1, SEQ ID 5, par. 0006).
Huang et al. (US 9428802 B2) teaches a chimeric primer, but does not teach or suggest the replacement of DNA bases with corresponding RNA bases to minimize or eliminate the formation of primer dimers.
Heller et al. (US 2015/0031086 A1) teaches a primer sequence with at least two adjacent LNA bases (par. 0044), however these primers are specifically designed to have a terminal mismatch primer-dimer structure (par. 0031, 0044) and are not designed by replacing two adjacent DNA bases with corresponding RNA bases.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Randi L Beil whose telephone number is (571)272-1147. The examiner can normally be reached M-F 8:00 am - 5:00 pm.
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/R.L.B./Examiner, Art Unit 1684
/AARON A PRIEST/Primary Examiner, Art Unit 1681