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
This Office Action is in response to Applicant’s Response to Election/Restriction Requirement. Applicant’s election without traverse of Group l (claims 1-6,8-15,17,18,23-28) drawn to a kit for sequencing application in the reply filed on 1/26/26 is acknowledged.
Claims 29,44,48,51, and 81 are canceled by the applicant.
Claims 1-6,8-15,17,18,23-28, and newly added claims 91-95 are pending.
Information Disclosure Statement
The information disclosure statements (IDS) documents submitted on 8/11/23, 9/6/23, 10/19/23, and 1/26/26 have been considered by the examiner.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2). Color drawings were
filed in the application without an accompanying petition, proper 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 4-6, 8-12, 91, 93 and 95 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.
Claims 4 recites the limitation " the third type of unlabeled nucleotide comprises a mixture of the third type of unlabeled nucleotide comprising the first hapten and the third type of unlabeled nucleotide comprising the second hapten" . The repetition of “the third type of unlabeled nucleotide” renders the claim language unclear as to what constitutes the mixture of the third type of unlabeled nucleotide. Claims 5, 6, 8-12, 91, 93, and 95 are rejected in virtue of dependency and failure to further clarify the issue.
Claim Rejections - 35 USC § 103
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 1-6, 9-15 ,18, 23-26, 91-95 is/are rejected under 35 U.S.C. 103 as being unpatentable over Iavicoli et. al. (WO 2022243480 A1, Filed 5/19/22) in view of Kain et. al. (US 20130079232 A1, Published 3/28/13, IDS Ref).
The applied reference has a common assignee with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Iavicoli teaches one, two, three, or four unlabeled nucleotides in an aqueous solution with an affinity reagent that specifically binds to the incorporated dNTP. The affinity reagents may include small molecules or protein tags that may bind to a hapten moiety of the nucleotide (such as streptavidin-biotin, anti-DIG and DIG, anti-DNP and DNP). Paragraph [0152] recites an exemplary embodiment that combines all three nucleotides, is a fluorescent-based SBS method that uses a first nucleotide type that is detected in a first channel when excited by a first excitation wavelength, and a second nucleotide type that is detected in a second channel when excited by a second excitation wavelength. The different type of nucleotides are labeled with different dye compounds that are spectrally distinguishable fluorescent dyes that may be excitable by a blue light (e.g., about 450 nm to about 460 nm) or a green light (e.g., about 520 nm to about 540 nm). The 4 nucleotides and hapten moieties of the reference encompass the limitations of claim 1 in which the first and second type of unlabeled nucleotide comprise a hapten. Iavicoli further teaches that the kit containing the unlabeled nucleotides may be used with a set of one or more detectable labels, implying the use of a third hapten for the third unlabeled nucleotide is optional ([0183], [0140], instant claim 1).
Iavicoli teaches that the hapten moiety of the unlabeled nucleotide may be attached to the nucleobase through a cleavable linker ([0092], applied to instant claims 2, 3, 5, 14, 92, and 94).
Iavicoli teaches that a combination of nucleotides may be provided as separate individual components or as a nucleotide mixture. After incorporation of an unlabeled nucleotide, an affinity reagent is then introduced that specifically binds to the incorporated nucleotide and the affinity reagents may include small molecules or protein tags that may bind to a hapten moiety of the nucleotide. The examiner is interpreting the unlabeled nucleotides within the mixture of the third type of unlabeled nucleotide of the instant claims as comprising a hapten and capable of specific binding to incorporated affinity reagents ([0176], [0091], [0092]; applied to instant claims 4, 12, and 93).
Iavicoli teaches the affinity reagents may include small molecules or protein tags that may bind to a hapten moiety of the nucleotide (such as streptavidin-biotin, anti-DIG and DIG, anti-DNP and DNP) ([0092], applied to instant claims 9, 11).
Iavicoli teaches the third type of unlabeled nucleotide comprises a third hapten, and the set of affinity reagents further comprises a third affinity reagent comprising a third hapten-binding partner that is capable of specific binding to the third hapten ([0091], [0092], instant claim 13).
Iavicoli teaches a kit may be used with a set of affinity reagents comprising one or more detectable labels and that one type of labeled nucleotides can be excited at a first wavelength, a second type of labeled nucleotides can be excited at a second wavelength, and a third labeled nucleotide can be excited at both the first and the second wavelength. The third labeled nucleotide can be excited at both the first and second wavelength, equating to a third affinity label comprising one or more of the first and second detectable labels of instant claim 23 ([0177], [0183]).
Iavicoli teaches a plurality of affinity reagents can contain small molecules or protein tags that may bind to a hapten moiety of the nucleotide and one affinity reagent may be labeled with multiple copies of the same fluorescent dyes. The kit may be used with a set of affinity reagents comprising one or more detectable labels, particularly those that may be excitable by blue or green light. Iavicoli further teaches that the dyes are conjugated to the nucleotide by covalent attachment via a linker and the dye compounds are spectrally distinguishable fluorescent dyes ([0092],[0122],[0140],[0177], instant claim 24).
Iavicoli teaches a fourth nucleotide type that lacks a label that is not, or minimally, detected in either channel. Paragraph [0091] states “After incorporation of an unlabeled nucleotide, an affinity reagent is then introduced that specifically binds to the incorporated dNTP to provide a labeled extension product comprising the incorporated dNTP “. The examiner interprets the absence of a label on the fourth nucleotide equal to the absence of dye, indicating the inability of specific binding to the affinity reagent for detection ([0152], applied to instant claims 25 and 93).
Iavicoli teaches a step of contacting a copy polynucleotide/target polynucleotide complex with one or more unlabeled nucleotides that each comprise a 3' blocking group ([0091], instant claim 26).
Iavicoli teaches affinity reagents that include hapten-binding partners such as streptavidin-biotin, anti-DIG and DIG, anti-DNP and DNP) and a fourth nucleotide type that lacks a label that is not, or minimally, detected in either channel ([0092], [0152], applied to instant claims 91, 93, and 95).
Iavicoli does not teach the third type of unlabeled nucleotide or first hapten comprising a biotin moiety, a third type of unlabeled nucleotide comprising a DIG or DNP moiety (limitations of instant claims 6, 10, 12, 15 and 93). However, Kain teaches an embodiment in which the hapten is selected from the group consisting of biotin, digoxigenin (DIG) and dinitrophenol (DNP) and the hapten binding partner is streptavidin ([0018] ,[0116], instant claims 6, 10, 12, 15, 18 and 93).
It would have been obvious to one having ordinary skill in the art before the
effective filing date of the claimed invention to have modified the teachings of Iavicoli to incorporate the teaching of Kain to select a DIG, DNP, or Biotin moiety molecular tag to allow for high-affinity detection of the nucleobases on the unlabeled nucleotide when paired with their specific binding partners. Incorporating these haptens in a kit provide the benefit of low cost, increased sensitivity, and efficiency for sequencing.
Claim(s) 28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Iavicoli et. al. (WO 2022243480 A1, Filed 5/19/22) and Kain et. al. (US 20130079232 A1, Published 3/28/13, IDS Ref) as applied to claims 1-6, 9-15 ,18, 23-26, 91-95 above, and further in view of Shendure et. al. (WO 2019236599 A2, Filed 6/4/19).
The teachings of Iavicoli and Kane are discussed above. Iavicoli and Kane fail to teach a kit comprising a DNA polymerase or one or more buffer compositions. However, Shendure teaches an embodiment where the nucleic acid fragments are prepared with single overhanging nucleotides by, for example, activity of certain types of DNA polymerase such as Taq polymerase and that optionally, other components such as buffers and solutions can be included in the kit. Useful buffers are those that promote cell lysis but retain nuclei integrity. An example of a cell lysis buffer includes 10 mM Tris-HCl, pH 7.4, 10 mM NaCl, 3 mM MgCl2, 0.1% IGEPAL CA-630, 1% ([00103], [00152], [00221], instant claim 28).
It would have been obvious to one having ordinary skill in the art before the
effective filing date of the claimed invention to have modified the teachings of Iavicoli and Kain to incorporate the teaching of Shendure by adding in a DNA polymerase for the purpose of accurately and efficiently replicating the DNA strand in a sequencing by synthesis (SBS) process, and the addition of a buffer solution to create the optimal chemical environment for efficient and accurate synthesis.
Claim(s) 8 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Iavicoli et. al. (WO 2022243480 A1, Filed 5/19/22) and Kain et. al. (US 20130079232 A1, Published 3/28/13, IDS Ref) as applied to claims 1-6, 9-15 ,18, 23-26, 91-95 above, and further in view of Johnson (US 20030219838 A1, Published 11/27/03).
The teachings of Iavicoli and Kane are discussed above. Iavicoli and Kane fail to teach blocking of one or more biotin binding sites of the avidin with a biotin moiety- containing molecule or analog. However, Johnson teaches that both egg white avidin and streptavidin are tetrameric proteins in which the biotin binding sites are arranged in pairs on opposite faces of the avidin molecule. In an example containing avidin beads placed in a BioRad column, to block tetrameric avidin sites, the column was washed with 0.6 ml 2 mM biotin in PBS, washed with 0.6 ml 100 mM glycine pH 2.8, and washed further with 1.2 ml 2.times.PBS to return the column to pH 7.2 ([0031], [0076], instant claims 8 and 17).
It would have been obvious to one having ordinary skill in the art before the
effective filing date of the claimed invention to have modified the teachings of Iavicoli and Kain to incorporate the teaching of Johnson to block the biotin binding sites of the avidin to reduce non-specific binding of unwanted biotinylated molecules in order to influence binding of target molecules and increase sequence specificity and nucleotide detection.
Claim(s) 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Iavicoli et. al. (WO 2022243480 A1, Filed 5/19/22) and Kain et. al. (US 20130079232 A1, Published 3/28/13, IDS Ref) as applied to claims 1-6, 9-15 ,18, 23-26, 91-95 above, and further in view of Romanov et. al. (US12110546B2, Published 9/3/20, IDS Ref).
The teachings of Iavicoli and Kane are discussed above. Iavicoli and Kane fail to teach the first detectable label dye formula as claimed in the instant application. However, Romanov teaches an example of a tertiary amine-substituted coumarin dye with the claimed structural formula (I) where R1 is -C(O)O C1-C6 alkyl ([C9/L60], instant claim 27).
It would have been obvious to one having ordinary skill in the art before the
effective filing date of the claimed invention to have modified the teachings of Iavicoli and Kain to incorporate the teaching of Romanov to incorporate a Coumarin dye into the sequencing kit for nucleotide labeling. The tertiary amine substituted coumarin dyes exhibit strong fluorescent characteristics in aqueous environments, making them a strong suitable choice for nucleotide labeling and sequencing application.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Avanda Harvey-Butler whose telephone number is (571)272-6511. The examiner can normally be reached M-F, 9-5 ET.
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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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/AVANDA E. HARVEY-BUTLER/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683