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 .
The supplemental claims filed 1/2/2024 are under consideration.
Priority
The present application is a 371 national stage entry of PCT/US2021/060647 (filed 11/23/2021).
Priority to US provisional applications:
63/116,997; 63/126,414; 63/157,924; 63/183,876, 63/222,963; and 63/234,635;
is not recognized because the documents do not disclose at least one of the following “elements”: “recognition elements” that may be “transformed” into “circular recognition elements”.
Priority to the ‘647 PCT application is recognized.
Information Disclosure Statement
The listing of references in the specification or the citation of references throughout 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 or cited on a submitted IDS, they have not been considered.
One of the IDS dated 4/8/2025 has been lined through in its entirety because it is a duplicate of the other IDS filed 4/8/2025.
Specification
The abstract of the disclosure is objected to because the it exceeds 150 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
Claim Rejections - 35 USC § 112
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.
Claim 2 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 2 requires an “exonuclease cleanup step” after the “rolling circle amplification” element of step (d).
The instant specification does not describe how to perform an exonuclease cleanup step in the presence of a rolling circle amplification product, which would be single stranded. The instant specification does not describe how to protect a rolling circle amplification product from exonuclease activity. One would have not reasonably found applicant to be in possession of a method in which a rolling circle amplification product is subjected to exonuclease treatment.
The instant specification fails to provide support for claim 2 in view of the 1/2/2024 supplemental amendments to the claims. The instant specification describes subjecting PCR reactions to exonuclease treatment to remove unused primers, unreacted probes and other single-stranded nucleic acids, but not double-stranded PCR products. The instant specification describes treating circularized probes to exonuclease treatment to remove single-stranded targets, but this is prior to amplification of the circularized probe sequences. Thus, claim 2 in view of the amendments to claim 1 encompasses new matter.
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.
Claim 12 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.
Regarding claim 12, the claim states a “3-ary nucleotide alphabet comprising A, C, G and T”. There is a disconnect between identifying an element as a “3-ary nucleotide alphabet” and then saying it is comprised of four different elements. The claim appears to be inconsistent regarding the common meaning of such terms.
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.
Claim(s) 1, 3, 5, 9, 10, 12, 13, 14, 23, 41, 157, 158, 159 and 160 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Zhang (WO 2017/177017).
Regarding claim 1, Zhang teaches providing a sample with a target and hybridizing a capture pair to the target nucleic acid as a “recognition element”.
Zhang further teaches the capture pair is then circularized or “transformed” into a “circular recognition element” using a variety of methods.
Zhang teaches the circular molecule includes a primer binding site and using rolling circle amplification to produce a long concatemer extension product suitable for sequencing. See p. 40, lines 10-21.
Zhang teaches the amplified circular molecule is detected using sequencing (p. 40, line 22-25).
Zhang further teaches the “recognition element” includes a “code” from a set in the form of a Zip barcode (p. 41, lines 5-30).
Regarding claim 3, Zhang teaches “counting” barcodes and “estimating” the quantity of the target by scoring the variant/SNP and Zip barcode (p. 41, lines 12-30). See also, p. 48, lines 1-8.
Regarding claim 5, Zhang teaches the barcodes have a length of 3 to 30 nucleotides, inclusive (p. 21, lines 28-30).
Regarding claim 9, Zhang teaches the barcodes are homopolymer free (p. 21, lines 18-27).
Regarding claim 10, Zhang teaches barcode sequences, such as GTCAGTCAGTCA (p. 21, lines 18-27), which has all the structural elements of code formed from a 4-ary nucleotide alphabet of A, C, G and T.
It is noted that claim 10 does not require an active method step of generating a set of codes. The language is interpreted as describing the structure of the codes based on how they are made. The claim broadly encompasses any code having the structure implied by the process, regardless of how the codes of the prior art are made.
Regarding claim 12, Zhang teaches barcode sequences, such as GTCAGTCAGTCA (p. 21, lines 18-27), which has all the structural elements of code formed from a 3-ary nucleotide alphabet comprising A, C, G and T.
It is noted that claim 12 does not require an active method step of generating a set of codes. The language is interpreted as describing the structure of the codes based on how they are made. The claim broadly encompasses any code having the structure implied by the process, regardless of how the codes of the prior art are made.
Regarding claim 13, Zhang teaches barcode sequences, such as GTCAGTCAGTCA (p. 21, lines 18-27), which has all the structural elements of code generated using a “4-state encoding trellis with 3 transitions per state”.
It is noted that claim 13 does not require an active method step of generating a set of codes. The language is interpreted as describing the structure of the codes based on how they are made. The claim broadly encompasses any code having the structure implied by the process, regardless of how the codes of the prior art are made.
Regarding claim 14, Zhang teaches the “recognition elements” includes a universal primer “associated” with the “code” (p. 22, lines 10-31; p. 23, lines 1-7).
Regarding claim 23, Zhang ligating the termini of the capture pair using the target as a guide to orientate the termini in the proper orientation (Fig. 1 and 2).
Regarding claim 41, Zhang teaches the target may be part of an aneuploidy (p. 7, lines 1-5; p. 24, lines 7-11).
Regarding claim 157, Zhang teaches the sequencing uses fluorescent nucleotides or oligonucleotides which involves measuring fluorescent in order to sequence the molecules (p. 4, lines 5-10; p. 37, lines 7-16).
Regarding claim 158, Zhang teaches the “coded targets” include a universal priming sequence (p. 38, line 11-15) as a “sequencing adapter” and performing sequencing as noted above.
Regarding claim 159, Zhang teaches immobilizing the “amplified codes” of the rolling circle amplification for sequencing (p. 46, lines 9-16; p. 53, lines 8-18) and measuring fluorescence as part of the sequencing process as noted above.
Regarding claim 160, Zhang teaches the method is performed in a well of a substrate (p. 19, lines 20-25).
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 38, 39, 40, 156 and 161 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhang (WO 2017/177017) in view of Shapero (WO 2018/223053 A1).
Regarding claims 38, 39, 40, 156 and 161, Zhang teaches providing a sample with a target and hybridizing a capture pair to the target nucleic acid as a “recognition element”.
Zhang further teaches the capture pair is then circularized or “transformed” into a “circular recognition element” using a variety of methods.
Zhang teaches the circular molecule includes a primer binding site and using rolling circle amplification to produce a long concatemer extension product suitable for sequencing. See p. 40, lines 10-21.
Zhang teaches the amplified circular molecule is detected using sequencing (p. 40, line 22-25).
Zhang further teaches the “recognition element” includes a “code” from a set in the form of a Zip barcode (p. 41, lines 5-30).
While Zhang teaches the above method, Zhang does not teach the additional element specific to claims 38, 40, 156 and 161.
However, Shapero teaches the molecular inversion probes, such as those used by Zhang, may be to analyze variants including SNPs, haplotype methylation patterns, insertions, deletions, and the like (para. 126). Shapero further teaches sets of 1,000 molecular inversion probes for 1,000 targets (para. 40, 146 and 147).
It would have been obvious to the ordinary artisan at the time of filing to have modified the method of Zhang by detecting different types of variants using the probes of Zhang and/or detecting hundreds of targets. The modifications have a reasonable expectation of success as each one is an obvious variant in of the teaching of Shapero that demonstrate the each are functionally equivalent as they detect a variant of interest.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH G DAUNER whose telephone number is (571)270-3574. The examiner can normally be reached 7 am EST to 4:30 EST with second Fridays 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, Wu-Cheng Winston Shen can be reached at 5712723157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JOSEPH G. DAUNER/Primary Examiner, Art Unit 1682