Detailed Office 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 .
Status of the Claims
Acknowledgement is hereby made of receipt and entry of the communication filed 29 December, 2025. Claims 59-61 and 65-81 are pending in the instant application.
37 C.F.R. § 1.84
The drawings filed 29 December, 2025, have been reviewed and are acceptable.
35 U.S.C. § 112(b)
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 previous rejection of claims 65 and 66 under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention, is hereby withdrawn in response to Applicant’s amendment.
35 U.S.C. § 112(a)
The following is a quotation 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.
Written Description
The previous rejection of claims 51-55, 57, and 58 under 35 U.S.C. § 112(a), as failing to comply with the written description requirement, is moot in view of the cancelation of these claims.
The previous rejection of claims 59 and 60 under 35 U.S.C. § 112(a), as failing to comply with the written description requirement, is hereby withdrawn in response to Applicant’s amendment and arguments.
Claims 65, 66, and 77-81 are rejected under 35 U.S.C. § 112(a), 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, at the time the application was filed, had possession of the claimed invention. Amgen, Inc. v. Sanofi, 872 F.3d 1367, 124 U.S.P.Q.2d 1354 (Fed. Cir. 2017). AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., 759 F.3d 1285, 111 U.S.P.Q.2d 1780 (Fed. Cir. 2014). Univ. of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 920, 69 U.S.P.Q.2d 1886, (Fed. Cir. 2004). Enzo Biochem, Inc. v. Gen-Probe, Inc., 296 F.3d 1316, 63 U.S.P.Q.2d 1609, (Fed. Cir. 2002). Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 U.S.P.Q.2d 1398, (Fed. Cir. 1997). Fiers v. Revel Co., 984 F.2d 1164, 25 U.S.P.Q.2d 1601, (Fed. Cir. 1993). Amgen, Inc. v. Chugai Pharmaceutical Co., 927 F.2d 1200, 18 U.S.P.Q.2d 1016, (Fed. Cir. 1991). In re Rasmussen, 650 F.2d 1212, 211 U.S.P.Q. 323 (C.C.P.A. 1981). In re Wertheim, 541 F.2d 257, 191 U.S.P.Q. 90 (C.C.P.A. 1976).
The crux of the statutory requirement governing written description is whether one skilled in the art, familiar with the practice of the art at the time of the filing date, could reasonably have found the later claimed invention in the specification as filed. In re Kaslow, 707 F.2d 1366, 1375, 217 U.S.P.Q. 1089, 1096 (Fed. Cir. 1983). In re Wilder, 736 F.2d 1516, 1520 222 U.S.P.Q. 349, 372 (Fed. Cir. 1984, cert. denied, 469 U.S. 1209 (1985). Texas Instruments, Inc. v. International Trade Comm’n, 871 F.2d 1054, 1063, 10 U.S.P.Q.2d 1257, 1263 (Fed. Cir. 1989). Moreover, the courts have stated that the evaluation of written description is highly fact-specific, and that broadly articulated rules are inappropriate. In re Wertheim, 541 F.2d 257, 263, 191 U.S.P.Q. 90, 97 (C.C.P.A. 1976). In re Driscoll, 562 F.2d 1245, 1250, 195 U.S.P.Q. 434, 438 (C.C.P.A. 1977). It is also important to remember that the true issue in question is not whether the specification enables one of ordinary skill in the art to make the later claimed invention, but whether or not the disclosure is sufficiently clear that those skilled in the art will conclude that the applicant made the invention having the specific claim limitations. Martin v. Mayer, 823 F2d 500, 505, 3 U.S.P.Q.2d 1333, 1337 (Fed. Cir. 1987).
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor has possession of the claimed invention. See, e.g., Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 U.S.P.Q.2d at 1116. An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 U.S.P.Q.2d 1961, 1966 (Fed. Cir. 1997). The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process. Fujikawa v. Wattanasin, 93 F.3d 1559, 1571, 39 U.S.P.Q.2d 1895, 1905 (Fed. Cir. 1996).
Determination of adequate written description requires the Examiner to read and analyze the specification for compliance with 35 U.S.C. § 112(a). In particular, each claim should be analyzed to determine its broadest reasonable interpretation consistent with written description. Each claim should be evaluated to determine if sufficient structures, acts, or functions are recited to make clear the scope and meaning of the claim, including the weight to be given the preamble. The entire application should be reviewed including the specific embodiments, figures, and sequence listings, to understand how applicant provides support for the various features of the claimed invention. The analysis of whether the specification complies with the written description requirement calls for the examiner to compare the scope of the claim with the scope of the description to determine whether applicant has demonstrated that the inventor was in possession of the claimed invention. Such a review is conducted from the standpoint of one of ordinary skill in the art at the time the application was filed (see, e.g., Wang Labs., Inc. v. Toshiba Corp., 993 F.2d 858, 865, 26 USPQ2d 1767, 1774 (Fed. Cir. 1993)) and should include a determination of the field of the invention and the level of skill and knowledge in the art. Finally, the Examiner should determine whether there is sufficient written description to inform a skilled artisan that the inventor was in possession of the claimed invention as a whole at the time of filing.
Claim 65 is directed toward a nucleic acid polymerase variant comprising substitution mutations at the following amino acid positions: S299, D300, 1301, D302, Y303, 1305, V306, E308, S312, 1313, S315, E317, L325, S327, K331, L335, F337, 1339, A340, N345, 1348, T350, D351, S355, S356, S357, L358, T360, Q361, E364, S367, V372, G375, 1379, S381, Q385, Q388, R390, Q393, 1398, S400, N404, S406, S408, T409, E410, S414, 1415, T418, T422, D423, Q425, S426, 1430, Q437, K438, 1439, R457, Q461, D462, 1464, C465, D466, Q468, E469, Y473, S474, F476, T477, D478, L481, K514, A641, Q750, K753, D755, and M794, wherein said numbering is based upon the Bst variant set forth in SEQ ID NO.: 1. Claim 66 references a polymerase variant comprising the following amino acid substitutions: S299A, D300K, I301M, D302A, Y303F, I305L, V306A, E308R, S312E, I313M, S315A, E317K, L325V, S327E, K331D, L335V, F337I, I339V, A340V, N345R, I348L, T350P, D351E, S355A, S356D, S357P, L358Q, T360V, Q361A, E364G, S367T, V372M, G375S, I379A, S381A, Q385K, Q388E, R390C, Q393S, I398L, S400A, N404D, S406A, S408G, T409V, E410D, S414A, I415A, T418M, T422E, D423A, Q425R, S426P, I430V, Q437R, K438A, I439V, R457W, Q461R, D462P, I464L, C465D, D466E, Q468R, E469R, Y473D, S474R, F476L, T477V, D478E, L481Q, K514R, A641T, Q750R, K753E, D755N, and M794I, wherein said numbering is based upon the Bst variant set forth in SEQ ID NO.: 1. Claims 77-81 are directed toward methods of detecting a target nucleic acid utilizing the polymerase variant of claim 65.
The Bst polymerase of SEQ ID NO. 1 (878 amino acids) comprises the following amino acid sequence:
MKKKLVLIDGNSIAYRAFFALPLLHNDKGIHTNAVYGFTMMLMKILEEEKPTHMLVAFDAGKTTFRHKTFEEYKGGRQQTPPELSEQFPLLRELLDAYRIRFYELENYEADDIIGTLCTKAEKEGFEVKVISGDRDLTQLASDHVTVDITKKGITDVESYTPETVQEKYGLTPEQIIDLKGLMGDKSDNIPGVPGIGEKTALKLLKEFGTIENILDSIEQVSGNKLRENLAKYRDIALMSKQLATILRDAPVDLSLEDIEYNGYDVDKVIALFKELGFNSLLEKMAAPQGEEETEVALSDIDYTIVDEVTESILSDEAALVVEVLESNYHKAPILGFAIA NEHGNFFIRTDTALSSSLFTQWLEDESKKKSVFDGKRAIVSLKWQGIQLRGVQFDLLIASYLLNPSQSTEDVASIAKTKQYTDVQSDEAIYGKGAKQKIPDEPVLAEHLVRKAAAIRALEQDFICDLQENEQYSLFTDLELPLSSILAEMEFTGVKIDVKRLKEMGEELTEQLKEIEQEIYELAGQEFNINSPKQLGVILFEKLQLPVLKKTKTGYSTSAEVLEKLAPQHEIVEKILHYRQLGKLQSTYIEGLLKVVHHDTNKVHTIFNQALTQTGRLSSTEPNLQNIPIRLEEGRKIRQAFVPSEPDWVIFSADYSQIELRVLAHIANDENLIDAFRHDLDIHTKTAMDIFHVNEDEVTPNMRRQAKAVNFGIVYGISDYGLSQNLNITRKEASEFIKRYFEIFPGVKQYMKDIVQEAKQKGYVTTLLHRRRYLPDITSRNFNLRSFAERTAMNTPIQGSAADIIKKAMIDLSNRLKKENMKARMLLQVHDELILEAPKEEVERLQQIVPEVMENAVQLRVPLKVDYHFGPTWYDAK. Other representative Bst polymerases set forth in the specification vary in lengths between 594 and 600 amino acids. However, the claims are not limited to any particular polymerase.
The broadest claims require the utilization of an inordinate number of polymerase variants. Considering claim 65, there are 77 different amino acids that can be substituted with any given amino acid which would encompass ~3 x 1098 variant sequences. While the disclosure provides a limited number of Bst mutants with the desired characteristics, nevertheless, it fails to provide a sufficient number of polymerase mutants to support the broadest claimed limitations. Other than the limited specific mutations recited, the disclosure fails to teach which portions of the polymerase should be targeted for modification. In terms of RT activity, only a limited number of mutants were characterized (e.g., A641T, A641T/M794I, D777N, S787R/F788R, F788R, M794I, M794I/R825H, 197, and M794I/197) and all of these mutants displayed lower activity as compared to Bst59 (see Fig. 1C). With respect to DNA polymerase activity, only a limited number of mutants were identified that displayed enhanced activity (e.g., A641T, A641T/M794I, M794I, 197, and M794I/197; see Fig. 1D). This finding is consistent with the state-of-the-art which teaches that identifying polymerase variants with improved properties can be challenging (Piotrowski et al., 2019; Oscorbin and Filipenko, 2023; Li et al., 2023). Piotrowski and colleagues screened thousands of DNA polymerase I mutants and were only able to identify a single mutant with increased activity. Oscorbin and Filipenko reviewed some of the biochemical properties of Bst polymerase including strand displacement, fidelity, replication slippage, terminal transferase activity, reverse transcriptase activity, exonuclease activity, thermal stability, DNA polymerase activity, and processivity. The authors noted that Bst is relatively poorly studied as compared to other DNA polymerases. Finally, Li and colleagues used molecular modeling to identify suitable mutational target sites in Bst. However, only a limited number of mutants were identified with enhanced activity, once again demonstrating the challenges associated with generating Bst polymerase mutants with enhanced characteristics. The disclosure only provides a limited number of mutants with enhanced DNA polymerase activity. However, this number was insufficient to put Applicant in possession of the full genus of Bst mutants.
Accordingly, when all the aforementioned factors are considered in toto, the skilled artisan would reasonably conclude that Applicants were not in possession of a sufficient number of polymerase variants at the time of filing to support the claim breadth.
Applicant argues that sufficient written support exists for the claimed genus of polymerase variants since the claims are directed toward substitution mutations at 77 different locations. This argument is not persuasive for the reasons of record set forth supra. The current claim language encompasses an inordinate number of variant polymerases that are neither contemplated nor described in the specification. A small finite number of Bst polymerase variants were generated. However, the specification fails to disclose the expression and characterization of a reasonable number of polymerase variants to support the claim breadth.
Allowable Subject Matter
Claims 59-61 and 67-76 appear to be free of the prior art of record and are allowable.
Action Is Final
Applicant’s amendment necessitated any and all new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See M.P.E.P. § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 C.F.R. § 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 C.F.R. § 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication should be directed to Jeffrey S. Parkin, Ph.D., whose telephone number is (571) 272-0908. The Examiner can normally be reached Monday through Friday from 10:00 AM to 6:00 PM. A message may be left on the Examiner's voice mail service. 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 are unsuccessful, the Examiner's supervisor, Michael Allen, Ph.D., can be reached at (571) 270-3497. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600.
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Respectfully,
/JEFFREY S PARKIN/Primary Examiner, Art Unit 1671
25 March, 2026