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 .
Claims 1-20 are currently pending and under examination.
Information Disclosure Statement
The Information Disclosure Statement filed October 16, 2024 has been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the terms Ion AmpliseqTM , Ion AmpliseqTM HD, OncomineTM Focus Assays and OncomineTM TCR Beta -LR assay (see Page 4, [0035] and Page 51, [00236]), which are trade names or a marks used in commerce, 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 Objections
Claim 15 is objected to because of the following informalities:
In claim 15, line 4, the term “substate” should read “substrate”.
Appropriate correction is required.
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.
Claims 1, 5-7, 12-15, 18 and 20 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Knapp et al. (United States Patent US 6,235,471 B1, patented May 22, 2001).
Regarding claim 1, Knapp teaches a method for sequencing a target polynucleotide secured to a substrate (Column 6, Lines 34-61, Column 7, Line 24—Column 8, Line 16, and Column 32, Lines 3-23). Knapp teaches detecting at a first zone of an assembly a first series of nucleotide incorporations complementary to at least a portion of the target polynucleotide, the first series of nucleotide incorporations forming a first complementary polynucleotide hybridized to the target polynucleotide, forming a double stranded polynucleotide (Column 6, Line 58—Column 7, Line 23, Column 7, Line 45—Column 8, Line16, Column 16, Lines 47-67, Column 21, Lines 27-30, Column 32, Liens 3-26, Column 41, Lines 6-18, Column). Knapp teaches moving the substrate to a second zone of the assembly (Column 7, Line 45—Column 8, Line 16, Column 28, Lines 48-67, Column 30, Line 60—Column 31, Line 2, Column 36, Lines 25-44, Column 39, Lines 46-63, Column 40, Lines 51-61, Column 41, Lines 6-18, Page 57, Lines 1-13, and Column 57, line 32—Column 58, Line 21). Knapp teaches denaturing the double stranded polynucleotide to recover the target polynucleotide and release the first complementary polynucleotide, the target polynucleotide remaining secured to the substrate (Column 16, Line 47—Column 17, Line 8, Column 17, lines 31-33, Column 21, Line 6—Column 22, Line 3, Column 32, Lines 2-54, Column 34, Lines 44-56, Column 58, Lines 25-57). Knapp teaches washing the first complementary polynucleotide from the substrate (Column 26, Lines 33-42, Column 32, Lines 3-17 and Column 58, Lines 25-57). Knapp teaches following the washing, moving the substrate to which the target polynucleotide is secured to the first zone and detecting a second series of nucleotide incorporations complementary to at least a portion of the target polynucleotide, the second series of nucleotide incorporations forming a second complementary polynucleotide (Column 6, Line 34—Column 7, Column 7, Line 45—Column 8, Line 23, Column 13, Line 56—Column 14, Line 10, Column 14, Lines 40-57, Column 26, Lines 33-42, Column 32, Lines 2-54, Column 28, Lines 48-67, Column 30, Line 60—Column 31, Line 2, Column 36, Lines 25-44, Column 39, Lines 46-63, Column 40, Lines 51-61, Column 41, Lines 6-18, Page 57, Lines 1-13 and Column 57, line 32—Column 58, Line 21).
Regarding claim 5, Knapp teaches denaturing includes melting by increasing a temperature to disassociate the first complementary polynucleotide and the target polynucleotide (Column 16, Line 61—Column 17, Line 8 and Column 20, Lines 19-37) .
Regarding claim 6, Knapp teaches adding a primer at least partially complementary to the target polynucleotide following the washing (Column 26, Lines 33-42 and Column 58, Lines 25-57).
Regarding claim 7, Knapp teaches adding the primer includes adding the primer while the substrate is disposed in the second zone (Column 7, Line 45—Column 8, Line 16, Column 28, Lines 48-67, Column 30, Line 60—Column 31, Line 2, Column 36, Lines 25-44, Column 39, Lines 46-63, Column 40, Lines 51-61, Column 41, Lines 6-18, Page 57, Lines 1-13, and Column 57, line 32—Column 58, Line 57).
Regarding claim 12, Knapp teaches the substrate includes an array of sensors (Column 13, Lines 11-16, Column 37, Lines 36-39, Column 41, Lines 40-46, Column 46, Line 45—Column 47, Line 5, Column 49, Lines 12-13, Column 54, Line 3-12). Knapp teaches the target polynucleotide secured in proximity to a sensor of the array of sensors (Column 13, Lines 11-16, Column 37, Lines 36-39, Column 41, Lines 40-46, Column 46, Line 45—Column 47, Line 5, Column 49, Lines 12-13, Column 54, Line 3-12).
Regarding claim 13, Knapp teaches engaging an adapter to the substrate when the substrate is disposed in the second zone (Column 25, Liens 62-67).
Regarding claim 14, Knapp teaches engaging a fluidic circuit with the substrate in response to moving the substrate to the first zone (Column 5, Lines 4-39 and Column 42, Lines 57-67).
Regarding claim 15, Knapp teaches securing the target polynucleotide to the substrate when the substrate is in the second zone and moving the substrate to the first zone prior to detecting the first series of nucleotide incorporations (Column 7, Line 45—Column 8, Line 16, Column 28, Lines 48-67, Column 30, Line 60—Column 31, Line 2, Column 36, Lines 25-44, Column 39, Lines 46-63, Column 40, Lines 51-61, Column 41, Lines 6-18, Page 57, Lines 1-13, and Column 57, line 32—Column 58, Line 57).
Regarding claim 18, Knapp teaches detecting includes pH-based detection (Column 54, Lines 15-27).
Regarding claim 20, Knapp teaches detecting includes fluorescence-based detection (Column 14, Lines 40-49, Column 54, Lines 15-27 and Lines 36-39 and Fig. 1).
Knapp teaches each and every limitation of claims 1, 5-7, 12-15, 18 and 20 and therefore Knapp anticipates claims 1, 5-7, 12-15, 18 and 20.
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 2-3, 8-11 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Knapp et al. (United States Patent US 6,235,471 B1, patented May 22, 2001), as applied to claims 1, 5-7, 12-15, 18 and 20 above, and in view of Davey et al. (United States Patent No. 10,273,540 B2, published April 30, 2019), cited on the IDS filed October 16, 2024.
Regarding claims 2-3, Knapp teaches a method for sequencing a target polynucleotide secured to a substrate as discussed above.
Regarding claim 8, Knapp teaches using multiple flow orders (Column 46, Line 45—Column 47, Line 5).
Regarding claims 9-11, Knapp teaches using detectable signals (Column 53, Line 40—Column 55, Line 6).
Regarding claim 19, Knapp teaches PH based detection as discussed above.
Knapp does not teach or suggest the second series of nucleotide incorporations is at least 97% or 99% the same as the first series of nucleotide incorporations. Knapp does not explicitly teach or suggest detecting the first series of nucleotide incorporations is performed using a first flow order of nucleotides and the second series of nucleotide incorporations is performed using a second flow order of nucleotides, and the first flow order is different from the second flow order. Knapp does not teach or suggest the detecting the first series of nucleotide incorporations and the detecting the second series of nucleotide incorporations produce first and second sets of signals. Knapp does not teach or suggest the method further comprising using the first and second sets of signals to determine an ordered set of base calls. Knapp does not teach or suggest using the first and second sets of signals includes averaging corresponding signals of the first and second sets of signals. Knapp does not teach or suggest averaging includes weighted averaging. Knapp does not teach or suggest pH-based detection includes detecting using an ion-sensitive field effect transistor formed in the substrate.
Davey teaches the different phase-states of the template population are represented in a phasing matrix, in which the flow cycles are represented on one axis and the different phase-states of the template strands are represented on the other axis (Column 8, Lines 17-33). Each entry in this matrix contains a value that is related to the number of template strands that occupy that phase-state at that particular flow cycle (Column 8, Lines 17-33). Davey teaches 6 flow cycles (Table 1A-B). Davey teaches a first flow order and a second flow order where in the flow orders are different from each other (Column 4, Lines 25-40 and Column 25, Lines 28-40). Davey teaches the second series of nucleotide incorporations is at least 97% the same as the first series of nucleotide incorporations (Column 10, Lines 19-48 and Table 1A-B). Davey teaches the second series of nucleotide incorporations is at least 99% the same as the first series of nucleotide incorporations (Column 10, Lines 19-48 and Table 1A-B). Davey teaches that the second series of nucleotide incorporations is at least 99% the same as the first series allows for more accurate estimates of signal correction that can be applied to the signal analysis (such as the measured signal data that accounts for effects that increase noise or blur the signal) used for base calling as taught by Davey (Column 7, Lines 43-54). Davey teaches the first series of nucleotides incorporations and the detecting the second series of nucleotides incorporations produce first and second sets of signals (Column 21, Lines 3-39). Davey teaches using the first and second sets of signals to determine an ordered set of base calls (Column 21, Lines 3-39). Davey teaches using a first and second set of signals includes averaging corresponding signals of the first and second sets of signals (Column 21, Lines 3-39). Davey teaches the averaging includes weighted averaging (Column 12, Lines 42-55). Davey teaches using to averaging data allows one to obtain region-wide (region size of 100x100 wells) estimate that quantitatively summarize the collection of signal data to analyze fitted signal correction parameters of multiple wells (Column 12, Lines 42-55). Davey teaches the substrate includes an array of sensors, the target polynucleotide secured in proximity to a sensor of the array of sensors. (Colum 18, Lines 28-51). Davey teaches engaging a fluidic circuit with the substrate (Fig. 7). Davey teaches the fluidic circuit allows for pH-based sequencing that includes multiple reservoirs for containing nucleotide reagents to be flowed for the sequencing process (Column 6, Lines 31-41). Davey teaches the ion concentrations can be mapped and represented in an ionogram which graphically represents the signals received from the sequencing operations after the raw data signals have been processed (Column 6, Lines 31-41). This raw data can be used for making base calls as taught by Davey (Column 6, Lines 31-41). Davey teaches detecting includes pH-based detection of nucleotide incorporations (Column 24, Lines 26-53). Davey teaches pH-based detection that includes detecting using an ion- sensitive field effect transistor formed in the substrate, specifically a chemFET sensor array (Column 24, Lines 7-25). Davey teaches the chemFET sensor array allows one to measure the amount of hydrogen ions released from the polymerase-catalyzed incorporation reactions (Column 6, Lines 31-41). Davey teaches in pH-based methods for DNA sequencing, base incorporations can be determined by measuring the hydrogen ions that are generated (Column 6, Lines 31-41). Davey teaches the production of hydrogen ions may be monotonically related to the number of contiguous complementary bases in the template strands (Column 6, Lines 31-41).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to have modified Knapp to incorporate the teachings of Davey where the second series of nucleotide incorporations is at least 99% the same as the first series of nucleotide incorporations. This allows for more accurate estimates of signal correction that can be applied to the signal analysis (such as the measured signal data that accounts for effects that increase noise or blur the signal) used for base calling as taught by Davey (Column 7, Lines 43-54).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to have modified Knapp to incorporate the teachings of Davey using a first and second set of signals from the array sensor, including averaging corresponding signals of the first and second sets of signals, including weighted averaging. This allows one to obtain region-wide (region size of 100x100 wells) estimate that quantitatively summarize the collection of signal data to analyze fitted signal correction parameters of multiple wells as taught by Davey (Column 12, Lines 42-55).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to have modified Knapp to incorporate the teachings of Davey to engage a fluidic circuit with the substrate in response to moving the substrate to the sequencing zone. The fluidic circuit allows for pH-based sequencing that includes multiple reservoirs for containing nucleotide reagents to be flowed for the sequencing process. The ion concentrations can be mapped and represented in an ionogram which graphically represents the signals received from the sequencing operations after the raw data signals have been processed. This raw data can be used for making base calls as taught by Davey (Column 6, Lines 31-41).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to have modified Knapp to incorporate the teachings of Davey to use pH-based detection of nucleotides that includes detecting using a chemFET sensor array. The chemFET sensor array allows one to measure the amount of hydrogen ions released from the polymerase-catalyzed incorporation reactions. In pH-based methods for DNA sequencing, base incorporations can be determined by measuring the hydrogen ions that are generated. The production of hydrogen ions may be monotonically related to the number of contiguous complementary bases in the template strands. The ion concentrations can be mapped and represented in an ionogram which graphically represents the signals received from the sequencing operations after the raw data signals have been processed. This raw data can be used for making base calls as taught by Davey (Column 6, Lines 31-41).
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Knapp et al. (United States Patent US 6,235,471 B1, patented May 22, 2001), as applied to claims 1, 5-7, 12-15, 18 and 20 above, and in view of Bowser et al. (WIPO International Publication WO 03/102212 A2, published December 11, 2003), cited on the IDS filed October 16, 2024.
Regarding claim 4, Knapp teaches denaturing as discussed above.
Knapp does not teach or suggest denaturing using a change in ionic strength to disassociate the first complementary polynucleotide and the target polynucleotide.
Bowser teaches removing includes denaturing using a change in ionic strength to disassociate the first complementary polynucleotide and the target polynucleotide. (Page 39, Lines 31-33 and Page 40, Lines 1-6, Page 46 Lines 28-33). Bowser teaches the ionic strength can have an impact on the separation efficiency (Page 40, Lines 29-33). Bowser teaches DNA binding interactions can vary greatly in sample solutions containing different amounts of salt (different ionic strengths) (Page 41, Lines 14-33). Davey teaches the binding between complementary DNA strands becomes stronger in high ionic strength solutions (Page 41, Lines 14-33). Davey teaches moreover, as the ionic strength of the buffer increases a lower concentration of the target is needed to completely bind to the template because of the enhanced binding (Page 41, Lines 14-33).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to have modified Knapp to incorporate the teachings of Bowser to remove the complementary polynucleotide and the target polynucleotide using change in the ionic strength. DNA binding interactions can vary greatly in sample solutions containing different amounts of salt (different ionic strengths). The binding between complementary DNA strands becomes stronger in high ionic strength solutions. Moreover, as the ionic strength of the buffer increases a lower concentration of the target is needed to completely bind to the template because of the enhanced binding as taught by Bowser (Page 41, Lines 14-33).
Claims 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Knapp et al. (United States Patent US 6,235,471 B1, patented May 22, 2001), as applied to claims 1, 5-7, 12-15, 18 and 20 above, and in view of Fonnum et al. (United States Patent No. 9,139,665 B2, published September 22, 2015), cited on the IDS filed October 16, 2024.
Regarding claim 16, Knapp teaches securing the target polynucleotide to the substrate includes forming the target polynucleotide on a polymer particle (Column 32, Lines 46-52, Column 39, Lines 16-19, Column 58, Lines 28-57). Knapp teaches using a well of the substrate (Column 28, Lines 48-64 and Column 30, Lines 63-67).
Regarding claim 17, Knapp teaches the target polynucleotide on the polymer particle as discussed above. Knapp teaches amplifying the target polynucleotide (Column 16, Lines 65-67).
Knapp does not teach or suggest explicitly depositing a polymer particle into a well of the substrate. Knapp does not teach or suggest amplifying the target polynucleotide on the polymer particle.
Fonnum teaches forming the target polynucleotide on a polymer particle (Fig. 2). Fonnum teaches depositing a polymer particle into a well of the substrate (Fig. 2). Fonnum teaches copying the target polynucleotide onto the polymer particle (Fig. 2). Fonnum teaches the polymer particle can be used as a solid support for polynucleotides (Column 14, Lines 4-17). Fonnum teaches amplifying the target polynucleotide on the polymer particle (Column 15, Lines 23-28). Fonnum teaches polymeric particles can be used in a variety of separations techniques and analytic techniques such as, the polymeric particles may be useful in binding polynucleotides (Column 14, Lines 4-17). Fonnum teaches such binding polynucleotides may be useful in separating polynucleotides from solution or can be used for analytic techniques, such as sequencing (Column 14, Lines 4-17).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to have modified Knapp to incorporate the teachings of Fonnum to form the target polynucleotide on a polymer particle, depositing the polymer particle into a well of the substrate and amplify the target polynucleotide on the polymer particle. Using these methods allows for the polymer particle to be used as a solid support for the polynucleotides and the polymeric particles may be useful in binding polynucleotides which may further be useful in separating polynucleotides from solution or can be used for analytic techniques, such as sequencing, as taught by Fonnum (Column 14, Lines 4-17).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-16 and 18-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,959,074.
Although the claims at issue are not identical, they are not patentably distinct from each other because the preambles are completely identical, it appears that the majority of steps of the claims are identical as well, so it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform a method for sequencing a target polynucleotide using those same steps. Therefore, the claims are not deemed to be patentably distinct.
Conclusion
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/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
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