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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/19/2026 has been entered.
Applicant’s cancellation of claim 26, amendment of claims 1 and 27, and the addition of new claim 28, in the paper of 12/19/2025, is acknowledged. Applicants' arguments filed on 12/19/2025, have been fully considered and are deemed to be persuasive to overcome some of the rejections previously applied. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. Claims 1-25, 27 and 28 are pending and at issue.
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(s) 1-25, 27 are 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim(s) 1-25, 27 are directed to all possible composition comprising: a plurality of engineered polymerases wherein individual engineered polymerases in the plurality comprise an amino acid sequence that is at least 90% identical to SEQ ID NO: 1 and comprise amino acid substitutions Aspl41Ala and Glul43Ala relative to SEQ ID NO: 1; a plurality of nucleic acid template molecules; and a plurality of oligonucleotide primers, wherein at least one of the individual engineered polymerases is a uracil-tolerant polymerase that exhibits increased uracil-tolerance compared to the wild-type Thermococci archaeon family B DNA polymerase of SEQ ID NO: 1. The specification, however, does not provides any representative species of that composition comprising: a plurality of engineered polymerases wherein individual engineered polymerases in the plurality comprise an amino acid sequence that is at least 90% identical to SEQ ID NO: 1 and comprise amino acid substitutions Aspl41Ala and Glul43Ala and exhibits increased uracil-tolerance, encompassed by these claims. There is no disclosure of any particular structure to function/activity relationship in between those polymerases having 90% identical to SEQ ID NO: 1 and comprise amino acid substitutions Aspl41Ala and Glul43Ala relative to SEQ ID NO: 1 and increased uracil-tolerance compared to the wild-type Thermococci archaeon family B DNA polymerase of SEQ ID NO: 1. The molecular mechanism of increased uracil tolerance is not associated with substitutions Aspl41Ala and Glul43Ala relative to a family B DNA polymerase (Zhang et al., Appl. Microbiol. Biotechnol. Vol 99, pp 6585-6597, 2015). The specification also fails to describe these family B DNA polymerases by any identifying structural characteristics or properties, for which no predictability of structure is apparent.
Regarding the level of skill and knowledge in the art of amino acid mutation, the reference of Singh et al. (Curr. Protein Pept. Sci. 18:1-11, 2017; cited on the attached Form PTO-892) reviews various protein engineering methods and discloses that despite the availability of an ever-growing database of protein structures and highly sophisticated computational algorithms, protein engineering is still limited by the incomplete understanding of protein functions, folding, flexibility, and conformational changes (see p. 7, column 1, top). Also, the unpredictability associated with amino acid mutations is exemplified by the reference of Zhang et al. (Structure 26:1474-1485, 2018; cited on the attached Form PTO-892), which discloses that even a mutation of a surface residue that was predicted to be benign caused significant structural changes and unexpected effects on the function of a polypeptide (p. 1475, column 1).
Given this lack of representative species as encompassed by the claims, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize Applicants were in possession of the claimed invention.
Applicant is referred to the revised guidelines concerning compliance with the written description requirement of U.S.C. 112, first paragraph, published in the Official Gazette and also available at www.uspto.gov.
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.
The rejection of claim(s) 1-4, 6, 8, 9 and 25 under 35 U.S.C. 103 as being unpatentable over Sorge et al., U.S. Patent No. 8,268,605 and Dombrowski et al., (Uniprot Accession No: A0A662NXP5, December 2020) is withdrawn based upon applicants argument presented in the paper of 12/19/2025.
Specifically applicants submission that the element of uracil tolerance of the engineered polymerase compared to the wild-type Thermococci archaeon Family B DNA polymerase of SEQ ID NO: 1, is a functional phenotype of the engineered polymerase that results in the ability of the engineered polymerase to replicate through uracil-containing templates without stalling or degradation is persuasive. Further applicants submission that this functional phenotype is not taught or suggested by Sorge alone or in combination with Dombrowski and applicants submission that, a mutation in the Exo I motif is structurally and functionally distinct from the modifications in a polymerase that confer uracil tolerance is found persuasive in overcoming the rejection.
The rejection of claim(s) 27 under 35 U.S.C. 103 as being unpatentable over Sorge et al., U.S. Patent No. 8,268,605 and Dombrowski et al., (Uniprot Accession No: A0A662NXP5, December 2020) as applied to claims 1-4, 6, 8, 9 and 25 above, and further in view of Sorge et al. (US 2004/0081965) is withdrawn based upon applicants amendment of the claim in the paper of 12/19/2025..
Claim(s) 1-6, 8, 9 and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sorge et al., (U.S. Patent No. 8,268,605), Sorge et al. (US 2004/0081965). and Dombrowski et al., (Uniprot Accession No: A0A662NXP5, December 2020).
Sorge et al. (U.S. Patent No. 8,268,605) teach a number of modified polymerases for improved incorporation of nucleotides and analogues and methods of their use in incorporating nucleotides into polynucleotides, particularly in the context of DNA sequencing. Sorge et al. (U.S. Patent No. 8,268,605) teach that the modified polymerases are Family B DNA polymerase, JDF-3 which is deficient in 3’ to 5’ exonuclease activity caused by the mutation in the “DXE” motif comprising D141A and E143A. Sorge et al. (U.S. Patent No. 8,268,605) teach methods of producing the mutant DNA polymerase comprising cloning and mutating the encoding gene and expression in a recombinant host cell. Sorge et al. (U.S. Patent No. 8,268,605) teach the isolation of the mutated DNA polymerase and its use in DNA synthesis methods comprising contacting the mutated polymerase with a nucleic acid template, nucleic acid primers and nucleotides under conditions that allow the formation of a polymerase complexed with the nucleic acid template and the nucleic acid primer.
Sorge et al. (US 2004/0081965) teach that unlike Taq, archaeal DNA polymerases (e.g., Pfu, Vent) possess a "read-ahead" function that detects uracil (dU) residues in the template strand and stalls synthesis. Uracil detection is thought to represent the first step in a pathway to repair DNA cytosine deamination (dCMP.fwdarw.dUMP) in archaea. Sorge et al. (US 2004/0081965 ) teach stalling of DNA synthesis opposite uracil has significant implications for high-fidelity PCR amplification with archaeal DNA polymerases. Sorge et al. (US 2004/0081965) disclose archael family B-type DNA polymerases with reduced base analog (uracil) detection activity. Specifically Sorge et al. (US 2004/0081965) disclose a Pfu DNA polymerase with reduced base analog activity comprises a substitution mutation at position V93 (i.e. V93R and V93E). Sorge et al. (US 2004/0081965) further teach that the mutant archael family B-type DNA polymerases may comprise a V93 (reduced uracil detection activity) and additional mutations that abolish one or more additional activities such as DNA polymerization activity or 3’-5’ exonuclease activity (see paragraphs [0081] thru [0085]) such as V93R/D141E/E143A triple mutant Pfu DNA polymerase with reduced 3'-5' exonuclease activity and reduced uracil detection activity and methods of their use for sequencing DNA (see claims 43 and supporting text).
Dombrowski et al., (Uniprot Accession No: A0A662NXP5, December 2020) teach the protein and encoding DNA sequence of a Family B DNA polymerase from Thermococci archaeon. Dombrowski et al. teach that this protein was isolated from Thermococci archaeon which was isolated from a hydrothermal sediment. The Family B DNA polymerase taught by Dombrowski et al. comprises an amino acid sequence which is 100% identical to the instant amino acid sequence of the polymerase of instant SEQ ID NO:1.
One of skill in the art before the effective filing date would have been motivated to substitute the polymerase taught by Dombrowski et al. for those taught by Sorge et al. (US 2004/0081965) and mutate them as taught by Sorge et al. (US 2004/0081965) comprising a reduced 3'-5' exonuclease activity and reduced uracil detection activity for their use in DNA sequencing methods and as a part of a composition comprising a nucleic acid template and primers. The obvious mutants would comprise the amino acid sequence of the Family B DNA polymerase from Thermococci archaeon comprising the amino acid sequence of SEQ ID NO:1 as taught by Dombrowski et al., reduced uracil detection activity (a V93E or V93R substitution) as taught by Sorge et al. (US 2004/0081965) and reduced 3’-5’ exonuclease activity (D141A and E143A substituttions) as taught by Sorge et al. (US 2004/0081965) and Sorge et al. (U.S. Patent No. 8,268,605). The motivation for substituting the polymerase taught by Dombrowski et al. is that they teach that the polymerase is a family B DNA polymerase and both Sorge et al. (US 2004/0081965) and Sorge et al. (U.S. Patent No. 8,268,605),. teach that family B DNA polymerase can be mutated with the D141A and E143A substitution to remove 3’ to 5’ exonuclease activity and reduced uracil detection activity (a V93E or V93R substitution) Sorge et al. (US 2004/0081965) for their use in DNA synthesis methods which allow the incorporating of nucleotide analogs. Further the teaching by Dombrowski et al. teach that this protein was isolated from Thermococci archaeon which was isolated from a hydrothermal sediment would have suggest that the protein has increased thermostability. The expectation of success his high based upon the high level of skill in the art of recombinant DNA technology as exemplified by Sorge et al.
Thus claim(s) 1-6, 8, 9 and 25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sorge et al., (U.S. Patent No. 8,268,605), Sorge et al. (US 2004/0081965). and Dombrowski et al., (Uniprot Accession No: A0A662NXP5, December 2020).
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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
The rejection of claims 1-24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of US 12,139,727 (Application No. 17/705,043) is withdrawn based upon applicants arguments presented in the paper of 5/29/2025.
The rejection of claims 1-24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6-8, 10-26, 28-35 of US 12,270,056) copending Application No. 17/705,020 (reference application, now allowed) is withdrawn based upon applicants arguments presented in the paper of 5/29/2025..
The rejection of claims 1-24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of copending Application No. 17/705,011 (reference application) is withdrawn based upon applicants arguments presented in the paper of 5/29/2025.
Claims 1-25, 27 and 28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of US 11,788,075. Although the conflicting claims are not identical, they are not patentably distinct from each other. Claims 1-22 of US 11,788,075, drawn to a composition comprising: a plurality of engineered polymerases comprising an amino acid sequence that is at least 85% identical to SEQ ID NO:1 and has at least one amino acid substitution: Asp141Ala or Glu143Ala, and a plurality of modified nucleotides comprising a removable chain terminating moiety at the 3′ carbon position of the sugar group anticipate instant claims 1-24 drawn to a composition comprising a plurality of engineered polymerases wherein individual engineered polymerases in the plurality comprise an amino acid sequence that is at least 90% identical to SEQ ID NO: 1 and comprise amino acid substitutions Asp141Ala and Glu143Ala relative to SEQ ID NO: 1; a plurality of nucleic acid template molecules; and a plurality of oligonucleotide primers.
Applicant has asked that this rejection be held in abeyance until the claims are deemed otherwise allowable.
Remarks
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RICHARD G HUTSON whose telephone number is (571)272-0930. The examiner can normally be reached 6-3 EST Mon-Fri.
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, Robert Mondesi can be reached on (408) 918-7584. 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.
rgh
1/13/2026
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652