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 claims dated 12/18/2023 are under consideration.
Priority
The present application is a 371 national stage entry of PCT/US2021/072219 (filed 11/3/2021), which claims benefit of US provisional application 63/109,819 (filed 11/4/2020). Priority 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.
On the 12/18/2023 IDS, Non-Patent Literature Documents listed as Cite Nos 16-19 have been lined through. The references are applications that have been published and when citing to a pending U.S. patent application that has been published under 35 U.S.C. 122(b) (eighteen-month publication), the USPTO prefers that the citation be to the patent application publication (by publication number) rather than to the application itself (by application number). It is also noted that 37 CFR 1.98(a)(2)(iii) requires a copy of a pending U.S. application that is being cited in an IDS if the cited information is not part of the specification, including the claims, and the drawings (e.g., an Office Action, remarks in an amendment paper, etc.). The reference to an application is considered to include information that is not part of the specification, such as Office Actions and Remarks in response to Office Actions that are part of the application prosecution history. An application is not static, but evolves over time during the course of prosecution. See MPEP 609.04(a). No material for these applications has been provided, and thus, they have not been considered.
The Examiner has included citations to US 2023/0407385, US 2024/0018599, US 2024/0309445, US 2024/0120025 and US 12,482,536 on the accompanying form PTO-892, which are the published forms of the applications and an issued patent based on one of the applications.
Drawings
High resolution copies of the drawings may be accessed via PAIR/Patent Center Retrieval using the Supplemental Content tab.
SEQ ID NOs for figures 14, 15 and 16 are provided in the specification.
Specification
The disclosure is objected to because of the following informalities: the specification includes “□” symbols in paragraphs 153, 258 and 262 of the original specification. It is unclear if these are intended to be used or are a typographical and/or conversion error of text.
Appropriate correction is required.
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 1-14, 16-17, 20-21, 23, 25-26 and 28-31 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.
Regarding claim 1, the claim recites “each flow step” of a plurality of first flow cycles. The instant specification describes a “flow cycle” being made of “repeating units” in paragraph 55. It is unclear what is the relationship between a “flow step” and a “plurality of first flow cycles” (emphasis added by the Examiner).
Regarding claim 1, the claim states “sequencing the second region” and recites three steps. It is unclear how the second region is subjected to “sequencing” when only “distance information indicative of length of the second region” is determined. In particular when more than one signal is detected, it is unclear how the sequence is determined as no association between a signal detected and they type of nucleotide is established in the claim.
Regarding claim 1, the claim recites “one or more labeled nucleotides of the plurality of nucleotides incorporated into the primer”. The recitation to “the plurality of nucleotides incorporated into the primer” lacks proper antecedent basis as no “incorporation” step is previously set forth. The recitation of “one or more labeled nucleotides” incorporated into the primer lacks proper antecedent basis as no labeled nucleotides are previously set forth in step (c).
Claims 2-11 depend from claim 1 and are rejected for the same reason.
Regarding claim 12, the claim recites “each flow step” of a plurality of first flow cycles. The instant specification describes a “flow cycle” being made of “repeating units” in paragraph 55. It is unclear what is the relationship between a “flow step” and a “plurality of first flow cycles” (emphasis added by the Examiner).
Claims 13-14, 16-17, 20-21, 23, 25-26 and 28-31 depend from claim 12 and are rejected for the same reason.
Regarding claim 20, the claim recites “the primer”. It is unclear if “the primer” is referring to “a primer” of step (b), step (c) or both steps (b) and (c).
Regarding claim 21, the claim recites “the primer”. It is unclear if “the primer” is referring to “a primer” of step (b), step (c) or both steps (b) and (c).
Regarding claim 23, the claim recites “the primer”. It is unclear if “the primer” is referring to “a primer” of step (b), step (c) or both steps (b) and (c).
Regarding claim 26, the claim recites “the primer”. It is unclear if “the primer” is referring to “a primer” of step (b), step (c) or both steps (b) and (c).
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) 1-14, 16-17, 20-21, 25-26 and 28-31 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Zhou (US 2014/0315724 A1).
Claim 1 recites a step (b) and a step (c). There is no indication in the claim if step (b) precedes step (c), step (c) precedes step (b) or if the steps may overlap in their performance.
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Regarding claim 1, Zhou teaches a method as depicted in Figs. 3, 4, 5 and 6. Fig. 5 is reproduced as being representative of the methods:
Zhou teaches providing a nucleic acid molecule 501 comprising two regions those complementary to regions 503, 504, 505 and/or 506.
Zhou sequences a first region complementary 503 (para. 96-97). The sequencing is done by sequencing by synthesis as described in para. 150, which involves detecting incorporated labeled nucleotides.
Zhou teaches sequencing a second region complementary 505 and/or 506. Zhou teaches 505 is the result of controlled extension (para. 98) and 506 is a sequencing by synthesis product (para. 98). For example, nucleotides are provided in cycles, e.g., using sets of nucleotides consists of one to three of the four types of nucleotides (e.g. for DNA polymerase, one, two or three of the four nucleotides dATP, dCTP, dTTP, dGTP) (para. 137), and after two or more cycles, extending 505, signals are detected as they are incorporated into 506. The distance between signals and the type of nucleotides indicates the lengths of 505 and/or 506. See also para. 123.
Regarding claims 2 and 3, Zhou teaches at least one or the two or more flow steps comprising the use of two, three or more different nucleotides simultaneously (para. 14, 15 and 60).
Regarding claim 4, Zhou teaches the primer is extended through 504 without detecting a signal as the nucleotides are natural nucleotides that are not labeled (para. 60).
Regarding claims 5 and 7, Zhou teaches “In one embodiment, multiple detection cycles can be performed using nucleotides with removable labels” (para. 191).
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. See MPEP 2123.
Here, a teaching of the use of removable labels reasonably teaches alternative embodiments in which labels that are not removable are used, methods in which removable labels are removed and/or not removed. Thus, Zhou reasonably teaches all the elements of claims 5 and 7.
Regarding claim 6, Zhou teaches detecting signals to identify bases after each round (para. 180), which for example, when there are 4 rounds, signals are detected every two rounds (rounds 1 and 3, rounds 2 and 4, etc.) (para. 17, 147, 180, 296). It is noted the claim does not exclude measuring signals in intervening flow steps between every 2 to 5. This collects a plurality of signals for incorporated bases which provide sequence information and distance information.
Regarding claim 8, Zhou teaches a combination of unlabeled and labeled nucleotides (para. 84 and 181).
Regarding claim 9, Zhou teaches controlled extending of 505 using native or unmodified nucleotides (para. 60 and 136) followed by using labeled nucleotides to sequence 506.
Regarding claim 10, Zhou teaches a combination of unlabeled and labeled nucleotides (para. 84 and 181).
Regarding claim 11, Zhou teaches controlled extending of 505 may involve labeled nucleotides (para. 136) followed by using labeled nucleotides to sequence 506.
Regarding claim 12, the claim is similar to claim 1 rejected above. The primary difference is that step (c) of claim 12 does not refer back to “the primer” of step (b).
However, the teachings of Zhou as applied to claim 1 equally apply to an embodiment of claim 12 in which the primers of steps (b) and (c) are the same primer.
Regarding claims 13 and 14, Zhou teaches at least one or the two or more flow steps comprising the use of two, three or more different nucleotides simultaneously (para. 14, 15 and 60).
Regarding claim 16, Zhou teaches “In one embodiment, multiple detection cycles can be performed using nucleotides with removable labels” (para. 191).
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. See MPEP 2123.
Here, a teaching of the use of removable labels reasonably teaches alternative embodiments in which labels that are not removable are used, methods in which removable labels are removed and/or not removed. Thus, Zhou reasonably teaches all the elements of claim 16.
Regarding claim 17, Zhou teaches a combination of unlabeled and labeled nucleotides (para. 84 and 181).
Regarding claim 20, Zhou teaches extending through first region 503 and then through second region 505 or 506 as depicted above.
Regarding claim 21, it is noted the claim does not define any structural orientation of the first and second regions. Thus, region 503 of Zhou is encompassed by the “second region” and region 505 or 506 is encompassed by the “first region”.
Alternatively, region 505 may be the “first region” and region 506 is the “second region”.
Regarding claim 25, Zhou teaches identifying sequences that are of the same nucleic acid versus those that are not using sequence reads (para. 125, 324, 331), which include “distance information” in the form of length and the order of nucleotides, e.g., the distance between adjacent bases or the distance between residues or motifs that are “determined” through alignments.
Regarding claim 26, Zhou teaches the above depicted method. The claim encompasses the method of Zhou when the “first region” is complementary to region 503, the “second region” is complementary to region 505 and the “third region” is complementary to region 506.
Regarding claims 28 and 29, Zhou teaches determining expected sequencing data using reference sequences and the information gathered from the order of bases added during rounds (para. 89, 90 and 168).
The “flow order” of a plurality of flow cycles broadly encompasses information reflecting the incorporated labeled bases added in a sequential manner. For example, if 4 different nucleotides are added in the order A, G, T, C, sequencing information reflects the relative order in which the nucleotides were added. A determined sequence of A-T-C demonstrates the flow order that C was added after A and T and T was added after A but before C.
Regarding claims 30 and 31, Zhou teaches detecting “expected” variants based on alignments with reference sequences and the information gathered from the order of bases added during rounds (para. 89, 90 and 168, 244 and 247-252).
The “flow order” of a plurality of flow cycles broadly encompasses information reflecting the incorporated labeled bases added in a sequential manner. For example, if 4 different nucleotides are added in the order A, G, T, C, sequencing information reflects the relative order in which the nucleotides were added. A determined sequence of A-T-C demonstrates the flow order that C was added after A and T and T was added after A but before C.
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) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Zhou (US 2014/0315724 A1) in view of Ronaghi (WO 2010/075188 A2).
Claim 23 recites a step (b) and a step (c). There is no indication in the claim if step (b) precedes step (c), step (c) precedes step (b) or if the steps may overlap in their performance.
Regarding claim 23, Zhou teaches a method as depicted in Figs. 3, 4, 5 and 6. Fig. 5 is reproduced as being representative of the methods above in the 102 rejections of claims 1 and 12.
Zhou teaches providing a nucleic acid molecule 501 comprising two regions, those complementary to regions 503, 504, 505 and/or 506.
Zhou sequences a first region 503 (para. 96-97). The sequencing is done by sequencing by synthesis as described in para. 150, which involves detecting incorporated labeled nucleotides.
Zhou teaches sequencing a second region complementary to 505 and/or 506. Zhou teaches 505 is the result of controlled extension (para. 98) and 506 is a sequencing by synthesis product (para. 98). For example, nucleotides are provided in cycles, e.g., using sets of nucleotides consists of one to three of the four types of nucleotides (e.g. for DNA polymerase, one, two or three of the four nucleotides dATP, dCTP, dTTP, dGTP) (para. 137), and after two or more cycles, extending 505, signals are detected as they are incorporated into 506. The distance between signals and the type of nucleotides indicates the lengths of 505 and/or 506. See also para. 123.
Zhou does not teach the specific additional elements of claim 23 not required by claim 12.
However, Ronaghi teaches using signal intensity to determine the distance of incorporation in a round of incorporation. For example, in Fig. 2, a 1x signal intensity indicates a distance of a single nucleotides, while a 2x signal intensity indicates a distance of two nucleotides and a single of 3x indicates a distance of three nucleotides.
It would have been prima facie to have modified the method of Zhou by incorporating the signal intensity analysis of Ronaghi, in particular in those embodiments of Zhou in which more than one nucleotide is added in a sequencing cycle/round.
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.
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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.
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/JOSEPH G. DAUNER/ Primary Examiner, Art Unit 1682