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 .
Priority
This application is a CON of 18/188,153 filed 03/22/2023 which is a CON of PCT/US2021/057600 filed 11/01/2021 which claims benefit of 63/108,179 filed 10/30/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/25/2024 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings were received on 8/22/2024. These drawings are found acceptable by the Examiner.
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 1-20 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.
(a) Claims 1-20 are indefinite at the recitation of “refined solution” in the claims 1 and 20 because it cannot be determined if merely reducing an amount of nucleotides comprising a 3’-OH from a nucleotide solution” results in “refined solution” or if selecting incorporating labeled nucleotides comprising a 3’-OH into a primer hybridized to a template with a depletion polymerase in a solution results in a “refine solution”. Neither the claims nor specification provide a clear limiting definition for what constitutes a “refine solution” and it cannot be determined how the recitation of “refined solution” as recited in the claim 1 and “refined solution” as recited in claim 20 are the same or if it is intended that they be different. Given the ambiguity, the metes and bounds of the limitation cannot clearly be ascertained. Clarification is required.
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 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 13-14, 16-19 of U.S. Patent No. 12116629 in view of McGall et al (US 20170016063).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the claims 1-20 of the instant invention and the claims 1-8, 13-14, 16-19 of U.S. Patent No. 12116629 encompass limitations that overlap with each other and recites steps involving (a) generating a refined solution comprising a reduced amount of nucleotides comprising a 3’-OH from a nucleotide solution, wherein said nucleotide solution comprises nucleotides comprising a 3’-OH and nucleotides comprising a 3’-reversible terminator moiety; and (b) contacting a primer hybridized to a target polynucleotide with the refined solution and incorporating with a sequencing polymerase a plurality of nucleotides, each nucleotide of the plurality comprising the 3’-reversible terminator moiety into the primer, contacting a primer hybridized to a template nucleic acid molecule with a refined solution comprising the labeled nucleotide, and incorporating the nucleotide into the primer, wherein the labeled nucleotide comprises a fluorescent dye; and detecting the fluorescent dye, thereby detecting the labeled nucleotide; wherein the refined solution is formed by selectively incorporating labeled nucleotides comprising a 3’-OH into a primer hybridized to a template with a depletion polymerase in a solution comprising labeled nucleotides comprising a 3’-OH and labeled nucleotides comprising a 3'-reversible terminator moiety.
While the limitations of the claims 1-20 overlap and embodies the limitations of claims 1-8, 13-14, 16-19 of U.S. Patent No. 12116629, the recited claims of US Patent No 12116629 do not recite all the recited limitations of the claims 1-20 including removal of the terminator moiety prior to incorporation of a next nucleotide.
Regarding claims 1-20, In a similar embodiment of the instant invention, McGall et al teach methods comprising contacting depletion polynucleotides, in the form of random primers in a mixture of nucleotides with a free 3’-OH (i.e., extendable native nucleotides), reversible terminated nucleotides, and depletion polymerase in the form of DNA polymerase (i.e., DNA Pol), which incorporates nucleotides into the depletion polynucleotides (i.e., random primers to form extension products (paragraph [0196]. The reference further teaches fluorescently labeled nucleotides ([0252], and labeled normal dNTP (i.e., having the claimed free 3’-OH group [0257]. Thus, it would have been obvious for the mixture of nucleotides with a free 3’-OH (i.e., extendable native nucleotides) and reversible terminated nucleotides to be labeled. McGall et al further teach the extended depletion polynucleotides (i.e., extension products) are stretched ([0196] wherein the stretching comprises extension by contacting with primers [0081] and polymerase to incorporate labeled nucleotides followed by sequences [0220] – [0222]. McGall also teach sequencing utilizing modified and labeled reversible terminators [0252] and [0258] and repeating extension using primers and a single labeled reversibly terminated base [0259]. McGall et al teach the use of TdT [0196] which is a depleting polymerase and further selective removal of terminator moiety in the assay ([0153]. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the claimed invention to have combined the teachings of the cited prior art with the claims of US Patent 12116629 to arrive at the instantly claimed method with a reasonable expectation of success. The ordinary artisan would have been motivated to make the combination because said combination would have resulted in a method having the added advantages of allowing real-time base-by-base measurement of temperate nucleic acid sequences as explicitly taught by McGall et al ([0249]. In addition, it would have been obvious to the ordinary artisan that the know techniques of the cited art could have been combined with predictable results because the known technique of the cited prior art predictably results in method steps useful for manipulating nucleic acid in sequencing and/or polymerizing assays.
It is noted that the courts have held that optimization through routine experimentation, and in particular, when related to differences in temperature, do support patentability (in re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)). Thus, the clamed temperature ranges merely represent routine optimization of the teachings of the cited prior art.
Closest prior art
10. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
(a) Gibbs et al (WO 9305183) teach multiplex assay for determining the sequence of a strand of DNA or RNA, comprising the steps of: attaching a plurality of DNA or RNA templates with annealed primers to a solid support; contacting the attached DNA or RNA templates with a reaction buffer, said buffer containing modified nucleotides and an enzyme to attach the modified nucleotides to the 3'- hydroxyl terminus of the primer attached to each DNA or RNA, wherein the modified nucleotides include a blocking group and a reporter, wherein the blocking group blocks the addition of further nucleotides to the primer and the reporter identifies which nucleotide has attached to the primer; removing unreacted modified nucleotides by washing said solid support with a first wash buffer; detecting the attached modified nucleotide added to each primer; removing the blocking group and reporter by contacting the DNA or RNA with a detaching buffer; contacting the attached DNA or RNA with a second wash buffer to remove traces of the detaching buffer; and repeating the above steps until the DNA or RNA has been sequenced (see claims at pages 19-22).
(b) McGall et al (US 20170016063) teach methods comprising contacting depletion polynucleotides, in the form of random primers in a mixture of nucleotides with a free 3’-OH (i.e., extendable native nucleotides), reversible terminated nucleotides, and depletion polymerase in the form of DNA polymerase (i.e., DNA Pol), which incorporates nucleotides into the depletion polynucleotides (i.e., random primers to form extension products (paragraph [0196]. The reference further teaches fluorescently labeled nucleotides ([0252], and labeled normal dNTP (i.e., having the claimed free 3’-OH group [0257]. Thus, it would have been obvious for the mixture of nucleotides with a free 3’-OH (i.e., extendable native nucleotides) and reversible terminated nucleotides to be labeled. McGall et al further teach the extended depletion polynucleotides (i.e., extension products) are stretched ([0196] wherein the stretching comprises extension by contacting with primers [0081] and polymerase to incorporate labeled nucleotides followed by sequences [0220] – [0222]. McGall also teach sequencing utilizing modified and labeled reversible terminators [0252] and [0258] and repeating extension using primers and a single labeled reversibly terminated base [0259]. McGall et al teach the use of TdT [0196] which is a depleting polymerase and further selective removal of terminator moiety in the assay ([0153].
While the cited prior art teaches various aspects of the instant invention, the cited prior art does not teach the combination of the method steps recited in the claims 1-20.
Conclusion
11. No claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CYNTHIA B WILDER whose telephone number is (571)272-0791. The examiner can normally be reached Flexible.
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/CYNTHIA B WILDER/Primary Examiner, Art Unit 1681
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