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 .
Election/Restrictions
Applicant’s election of Group I (claims 1-14) in the reply filed on 8/12/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is still deemed proper and is therefore made FINAL.
Status of Application, Amendments, And/Or Claims
Claims 1-16 are pending.
Claims 15-16 are withdrawn for being drawn to a non-elected invention (i.e., Group II).
Claims 1-14 are under examination.
Information Disclosure Statement
The Information Disclosure Statement filed on 10/11/2022 has been considered.
Claim Objections
Claim 12 is objected to because of the following informalities: claim 12 is objected for the use of an abbreviated phrase (dNTPs), which should be described for the first time followed by an abbreviated form placed in a bracket.
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because claims 1-14 are drawn to a composition comprising a naturally existing protein comprising a thermostable DNA polymerase comprising SEQ ID NO: 1 and a reaction buffer comprising 10 - 30 mM Tris-HCl, pH 8.5-9.0; 20-40 mM KCl; 5-15 mM (NH4)2SO4; 1.5-3.5 mM Mn2+;0.01-0.20% (w/v) gelatin and/or serum albumin; and 0.05-0.15% (w/v) of a nonionic detergent, with the proviso that no more than 0.1 mM Mg2+ is present in the composition. As such the reaction buffer of claim 1 is to support the stability or functionality of the naturally existing DNA polymerase. Upon further consideration of search results (see SRCH dated 11/4/2025), the examiner finds that the thermostable Polymerase exists in the nature for DNA synthesis and repair. The reference Asakura et al. teaches thermostable polymerase (J. Ferment. Bioeng. 76: 265-269 (1993), search Results 1, sequence alignment). Therefore, the inclusion of a buffer, salt or detergent to a composition of naturally existing protein would not make the invention patentable.
RESULT 1
DPO1T_THET8
ID DPO1T_THET8 Reviewed; 834 AA.
AC P52028; Q5SJF4;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 29-MAR-2005, sequence version 2.
DT 18-JUN-2025, entry version 145.
DE RecName: Full=DNA polymerase I, thermostable;
DE EC=2.7.7.7 {ECO:0000250|UniProtKB:P52026};
DE AltName: Full=Tth polymerase 1;
GN Name=polA; OrderedLocusNames=TTHA1054;
OS Thermus thermophilus (strain ATCC 27634 / DSM 579 / HB8).
OC Bacteria; Thermotogati; Deinococcota; Deinococci; Thermales; Thermaceae;
OC Thermus.
OX NCBI_TaxID=300852;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Asakura K., Komatsubara H., Soga S., Yomo T., Oka M., Emi S., Urabe I.;
RT "Cloning, nucleotide sequence, and expression in Escherichia coli of DNA
RT polymerase gene (polA) from Thermus thermophilus HB8.";
RL J. Ferment. Bioeng. 76:265-269(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 27634 / DSM 579 / HB8;
RA Masui R., Kurokawa K., Nakagawa N., Tokunaga F., Koyama Y., Shibata T.,
RA Oshima T., Yokoyama S., Yasunaga T., Kuramitsu S.;
RT "Complete genome sequence of Thermus thermophilus HB8.";
RL Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: In addition to polymerase activity, this DNA polymerase
CC exhibits 5'-3' exonuclease activity. {ECO:0000250|UniProtKB:P52026}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) +
CC diphosphate; Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:17339, Rhea:RHEA-
CC COMP:17340, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:173112;
CC EC=2.7.7.7; Evidence={ECO:0000250|UniProtKB:P52026};
CC -!- SIMILARITY: Belongs to the DNA polymerase type-A family. {ECO:0000305}.
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DR EMBL; D28878; BAA06033.1; -; Genomic_DNA.
DR EMBL; AP008226; BAD70877.1; -; Genomic_DNA.
Query Match 100.0%; Score 4266; Length 834;
Best Local Similarity 100.0%;
Matches 834; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MEAMLPLFEPKGRVLLVDGHHLAYRTFFALKGLTTSRGEPVQAVYGFAKSLLKALKEDGY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MEAMLPLFEPKGRVLLVDGHHLAYRTFFALKGLTTSRGEPVQAVYGFAKSLLKALKEDGY 60
Qy 61 KAVFVVFDAKAPSFRHEAYEAYKAGRAPTPEDFPRQLALIKELVDLLGFTRLEVPGYEAD 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KAVFVVFDAKAPSFRHEAYEAYKAGRAPTPEDFPRQLALIKELVDLLGFTRLEVPGYEAD 120
Qy 121 DVLATLAKKAEKEGYEVRILTADRDLYQLVSDRVAVLHPEGHLITPEWLWEKYGLRPEQW 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DVLATLAKKAEKEGYEVRILTADRDLYQLVSDRVAVLHPEGHLITPEWLWEKYGLRPEQW 180
Qy 181 VDFRALVGDPSDNLPGVKGIGEKTALKLLKEWGSLENLLKNLDRVKPENVREKIKAHLED 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VDFRALVGDPSDNLPGVKGIGEKTALKLLKEWGSLENLLKNLDRVKPENVREKIKAHLED 240
Qy 241 LRLSLELSRVRTDLPLEVDLAQGREPDREGLRAFLERLEFGSLLHEFGLLEAPAPLEEAP 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LRLSLELSRVRTDLPLEVDLAQGREPDREGLRAFLERLEFGSLLHEFGLLEAPAPLEEAP 300
Qy 301 WPPPEGAFVGFVLSRPEPMWAELKALAACRDGRVHRAADPLAGLKDLKEVRGLLAKDLAV 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 WPPPEGAFVGFVLSRPEPMWAELKALAACRDGRVHRAADPLAGLKDLKEVRGLLAKDLAV 360
Qy 361 LASREGLDLVPGDDPMLLAYLLDPSNTTPEGVARRYGGEWTEDAAHRALLSERLHRNLLK 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LASREGLDLVPGDDPMLLAYLLDPSNTTPEGVARRYGGEWTEDAAHRALLSERLHRNLLK 420
Qy 421 RLEGEEKLLWLYHEVEKPLSRVLAHMEATGVRLDVAYLQALSLELAEEIRRLEEEVFRLA 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 RLEGEEKLLWLYHEVEKPLSRVLAHMEATGVRLDVAYLQALSLELAEEIRRLEEEVFRLA 480
Qy 481 GHPFNLNSRDQLERVLFDELRLPALGKTQKTGKRSTSAAVLEALREAHPIVEKILQHREL 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GHPFNLNSRDQLERVLFDELRLPALGKTQKTGKRSTSAAVLEALREAHPIVEKILQHREL 540
Qy 541 TKLKNTYVDPLPSLVHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAF 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 TKLKNTYVDPLPSLVHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAF 600
Qy 601 VAEAGWALVALDYSQIELRVLAHLSGDENLIRVFQEGKDIHTQTASWMFGVPPEAVDPLM 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 VAEAGWALVALDYSQIELRVLAHLSGDENLIRVFQEGKDIHTQTASWMFGVPPEAVDPLM 660
Qy 661 RRAAKTVNFGVLYGMSAHRLSQELAIPYEEAVAFIERYFQSFPKVRAWIEKTLEEGRKRG 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RRAAKTVNFGVLYGMSAHRLSQELAIPYEEAVAFIERYFQSFPKVRAWIEKTLEEGRKRG 720
Qy 721 YVETLFGRRRYVPDLNARVKSVREAAERMAFNMPVQGTAADLMKLAMVKLFPRLREMGAR 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 721 YVETLFGRRRYVPDLNARVKSVREAAERMAFNMPVQGTAADLMKLAMVKLFPRLREMGAR 780
Qy 781 MLLQVHDELLLEAPQARAEEVAALAKEAMEKAYPLAVPLEVEVGMGEDWLSAKG 834
||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 MLLQVHDELLLEAPQARAEEVAALAKEAMEKAYPLAVPLEVEVGMGEDWLSAKG 834
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 factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1-14 are rejected under 35 U.S.C. 103 as being unpatentable over Gelfand et al. (AU 7244491 A) in view of Zou et al. (US 20050064426) and Asakura et al. (J. Ferment. Bioeng. 76:265-269(1993)).
The instantly claimed invention is broadly drawn to a composition, comprising: a recombinant thermostable DNA polymerase comprising SEQ ID NO:1 or a variant thereof having at least 99% identity to SEQ ID NO:1; and a reaction buffer, the reaction buffer comprising 10 - 30 mM Tris-HCl, pH 8.5-9.0; 20-40 mM KCl; 5-15 mM (NH4)2SO4; 1.5-3.5 mM Mn2+;0.01-0.20% (w/v) gelatin and/or serum albumin; and 0.05-0.15% (w/v) of a nonionic detergent, with the proviso that no more than 0.1 mM Mg2+ is present in the composition, wherein the reaction buffer further comprises chelating agent (claim 2-3), wherein the concentration of the chelating agent is 0.01-0.1 mM (claim 5), wherein the reaction buffer comprises 25 mM Tris- HCl, pH 8.8; 30 mM KCl; 10 mM (NH4)2SO4; 1.5-3.5 mM Mn2+; 0.1% (w/v) gelatin and/or serum albumin; and 0.1% (w/v) of a nonionic detergent (claim 6), wherein the reaction buffer further comprises chelating agent (claim 7-8), herein the concentration of the chelating agent is 0.01-0.1 mM (claim 10), wherein the reaction buffer comprises the nonionic detergent polysorbate 20 (claim 11). The composition of claim 1, further comprises dNTPs (claim 12), wherein the composition is liquid, frozen or lyophilized, and wherein the composition is stored in the range of - 80°C to 30°C.
Gelfand et al. teach a composition comprising thermostable DNA polymerase for PCR amplification (see abstract, page 1, paragraph 1). They teach adding dNTPs to the reaction mix to achieve DNA synthesis. They teach that dNTPs are in a concentration of 1- 800 µM each (page 18, lines 22+). They teach a composition comprising DNA polymerase and a divalent either Mn+2, Mg+2 or Co+2 that can activate DNA polymerases. They teach that a buffering agent comprises 0.5-2.5 mM MnCl2, or 0.5-10 mM MgCl2. They teach that the Tris-HCl concentration is 5-50 mM and the pH is 8.0-8.8 (see pg. 18, lines 27+). They adding dNTP to the reaction mix to achieve DNA synthesis. They teach that dNTPs are in a concentration of 1- 800 µM each (page 18, lines22+). They teach that a chelating agent EDTA is less than 0.5 mM. It is noted that the chelating agent EDTA, EGTA, DTPA, CDTA, NTA and HEDTA are functionally equivalent as evident by claim 3 or 7, and as disclosed at pg. 5 as chelating agents. They teach Tween 20 is present at approximately less than 0.1%, preferably 0.055-0.01% (page 18, lines 30+). They teach that the buffer for DNA polymerase can be included in about 0.5 ug/µl as a diluent (pg. 25, line 8). They teach that glycerol is present in a concentration of 1-10% in the reaction mix. They teach a kit for using DNA polymerase (see claims 31-40). They teach cleaning the DNA product and storing at -20°C (see page 28, line29). They teach effect of Mn2+ and Mg2+ on DNA synthesis and one skill in the art can optimize and they can be substituted for each other (see page 18, line3). They do not teach that the composition comprises (NH4)SO4 and that the DNA polymerase comprises amino acid sequence of SEQ ID NO:1.
Zou et al. teach DNA synthesis using DNA polymerase in a reaction that comprises Tris-HCl, KCl, MgCl2, 10 mM (NH4)SO4, and dNTPs. They use EDTA to terminate the reaction. Zou et al do not teach a polymerase having amino acid sequence of SEQ ID NO: 1.
The polymerase of amino acid sequence of SEQ ID NO: 1 is well known in the art (see sequence alignment above, under 35 USC 101 rejection), and it is taught by Asakura et al.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use a thermostable DNA polymerase as taught by Asakura et al. and would have included (NH4)SO4 as taught by Zou et al in a composition comprising Tris-HCl, pH 8.5-9.0, 5-15 KCl, with or without Mg2+, Mn2+, glycerol, and detergent as taught by Gelfand et al. Additionally, one would have been motivated to do so because Asakura et al teach that the DNA polymerase is thermos stable and has the functionality of DNA polymerase. Further, one would have a reasonable expectation of success in using DNA polymerase as taught by Asakura et al teach that the polymerase is thermostable and it has been routinely used in the art.
Generally, differences in concentrations of components of a formulation will not support the patentability of subject matter encompassed by the prior art. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Aller, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674