DETAILED ACTION
Notice of 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 Application
Claims 1, 3-5 and 7-14 are pending and are subject to examination on the merits.
Priority
The instant application is a 371 of PCT/KR2021/006654 filed 28 May 2021 which claims benefit of foreign priority documents KR 10-2020-0064838 and KR 10-2021-0068144 filed 29 May 2020 and 27 May 2021, respectively, are acknowledged. Said documents have been received.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 29 November 2022 has been considered by the examiner. See initialed and signed PTO/SB/08.
Specification
Compliance with Sequence Rules
The sequence listing, filed in computer readable form (CRF) on 29 November 2022, has been received and entered. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2) (ST.25). However, this application fails to fully comply with the requirements of 37 C.F.R. § 1.821 through 1.825 (ST.25).
The following Figures contain sequences that contain four or more specifically defined amino acids without any corresponding SEQ ID NO: and/or no reference to any SEQ ID NO: in the Brief Description of the Drawings.
In Figure 1, all six sequences in the alignment are required to have sequence identifiers (SEQ ID NO:).
In Figure 3, the Taq DNA Polymerase sequences is required to have a sequence identifier (SEQ ID NO:).
On p. 34, lines 27 and 28, two nucleotide sequences are disclosed without any corresponding sequence identifier (SEQ ID NO:).
* If the noted sequences are in the sequence listing as filed, Applicants must amend the specification (Brief Description of the Drawing) or Drawings themselves to identify the sequences appropriately by SEQ ID NO:. If the noted sequences are not in the sequence listing as filed, Applicants must provide (1) an updated copy of the sequence listing containing the requisite sequences in computer readable form (CRF), (2) an amendment directing its entry into the specification, (3) a statement that no new matter has been added and (4) an amendment to the specification or Drawing to identify the identified sequences by SEQ ID NO:, which can be in the Brief Description of the Drawings section of the specification and (5) an updated incorporation by reference statement with the new date of creation, sequence file name and size. – See also MPEP 2422.
The disclosure is further objected to because it contains embedded hyperlinks and/or other form of browser-executable code on p. 5, line 1; p. 42, line 35 and p. 43, line 3. 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.
Claim Objections
Claim 13 are objected to because of the following informalities:
The claim appears to have a typographical error in line two, where it recites “change” instead of “chain” (e.g. polymerase chain reaction). Appropriate correction is required.
Claim Rejections - 35 USC § 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.
Claims 1, 3-5, 7-12 are rejected 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.
Claim 1 recites introducing mutations into a DNA polymerase at various positions corresponding to those in SEQ ID NO: 1, which results “maintained polymerization activity and also enhanced discrimination of an allelic or genetic mutation compared with a wild-type DNA polymerase.”
However, given the claim construction, the comparison it made to any wild-type DNA polymerase not necessarily with the wild-type Taq DNA polymerase of SEQ ID NO: 1. Given there are an enormous number of wild-type DNA polymerases, it is thus unclear which wild-type enzyme the comparison is made. In addition, the specification also suggests the comparison is made to any wild-type polymerase and is not limited to a particular one such as wild-type Taq DNA polymerase of SEQ ID NO: 1.
Claims 1, 3-5, 7-12 are rejected 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.
Claim 1 recites that mutations are introduced into a DNA polymerase having homology of at least 80% identity to Taq DNA polymerase consisting of SEQ ID NO: 1 (Thermus aquaticus), or a Klenow fragment thereof. However, this is unclear because Klenow fragments are found in E. coli DNA polymerase I. While both polymerases share the basic function of synthesizing DNA and have 5’-3’ polymerase activity, the Klenow fragment lacks any 5’-3’ exonuclease activity found in Taq polymerase. In addition, Klenow fragments possess 3’-5’ exonuclease activity that is absent in Taq polymerase. As such, it unclear what is meant by a Klenow fragment of a Taq polymerase.
Claims 3-5 and 7-12 are included as they do not remedy the noted deficiency.
Clarification is requested.
Claim 10 is 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.
Claim 10 is dependent on claim 1 and recites specific substitutions at positions including E507 and K508 (among others). However, claim 1 does not recite positions 507 and 508 are one of the at least one positions selected for mutation. Thus, it is unclear if positions 507 and 508 were inadvertently left out of claim 1.
Despite this fact, claim 1 does not provide antecedent basis for substitutions at positions 507 and 508. (Notably those positions are acceptable in claim 9 because the DNA polymerase must have at least one substitution selected from the positions in claim 1, and further has at least one more substitution selected from the positions in claim 9).
Clarification is requested.
For examination purposes, it will be assumed positions 507 and 508 are meant to be included in claim 1. This is consistent with the specification as demonstrated in Table 1 and Table 3.
Claim 13 is rejected 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 join inventor regards as the invention. This is because the claim attempts to recite a process without setting forth any steps involved in the process. Specifically, the claim recites “using the DNA polymerase mutant of claim 1”, however, it is unclear what the process steps are supposed to be which results in said use in a RT-PCR reaction. It is noted, the recitation of a “use” without any active, positive steps delimiting how the use is practiced is deemed indefinite. See MPEP 2173.05(q).
Claim Rejections - 35 USC § 112(a)
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.
Claims 1, 3-5, 7-9, 11 and 13-14 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.
The MPEP in section 2163(I) states that the purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made/filed, of the specific subject matter claimed:
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonable conclude the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings.
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An applicant shows that the inventor was in 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. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997)"
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed. Circ. 1997).
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." Furthermore, the courts have also held that possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
The claims in their broadest are drawn to mutant/variant DNA polymerases, wherein the mutations occur in a DNA polymerase having at least 80% sequence homology to Taq DNA Polymerase consisting of SEQ ID NO: 1, or Klenow fragment thereof. The mutant must comprise at least one amino acid mutation in an amino acid corresponding to amino acids 497, 498, 499, 500, 501, 502, 503, 505, 506, 509, 510, 511, 512, 513, 514 and positions corresponding thereto in SEQ ID NO: 1. Said mutation(s) results in a DNA polymerase mutant that has maintained polymerization activity and also enhanced discrimination of an allelic or genetic mutation compared with a wild-type DNA polymerase. Thus, the way the claim is constructed, the mutated DNA polymerase can have an unlimited number of mutations, so long as the mutations are introduced into any DNA polymerase having at least 80% homology (interpreted as sequence identity). That is, the claim does not require that the resultant DNA polymerase with the claimed mutations are limited by the 80% identity to SEQ ID NO: 1, said 80% identity as noted only limits the starting DNA polymerase but not the ending mutant DNA polymerase. As such, the mutant DNA polymerases as claimed are drawn to a huge genus DNA polymerases which minimally require mutations in positions 497, 498, 499, 500, 501, 502, 503, 505, 506, 509, 510, 511, 512, 513, 514 and positions corresponding thereto in SEQ ID NO: 1, but which can comprise an unlimited number of additional mutations, which also must necessarily result in the requisite function of maintained polymerization activity and also enhanced discrimination of an allelic or genetic mutation. The specification, however, is very limited in the number of mutations that are introduced into one specific Taq DNA polymerase consisting of SEQ ID NO: 1. Said mutations are substitutions in positions G499R, K505G, K505I, K505L, K505M, K505F, E507A, E507G, E507S, E507R, E507Q, K508A, K508G, K508S, K511A, R512K, R512W only (See Table 3), wherein these substitution positions give rise to the claimed function. These very specific substitutions of Taq DNA polymerase, however, are not representative of the entire claimed genus of mutant DNA polymerases in terms of structure and the requisite function. Even though some DNA polymerases, like Taq DNA polymerases, are extremely well known and characterized, the claimed genus far exceeds the well-known and well characterized DNA polymerases; in addition to the required substitutions. As such, the specification does not provide adequate support for the claimed genus in terms of structure and function.
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, 3-5, 9-10 and 14 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a natural phenomenon) without additional elements that integrate the judicial exception into a practical application. An analysis with respect to the claims as a whole reveals that they do not include additional elements that integrate the judicial exception into a practical application. See MPEP 2106.
Analysis of subject-matter eligibility under 35 U.S.C. § 101 requires consideration of the following steps:
Step (1) whether the claim is directed to one of the four categories recited in §101 (process, machine, manufacture or composition of matter);
Step (Revised 2A - Prong 1) do the claims recite an abstract idea (mathematical concepts, mental processes or method of organizing human activity), law of nature or natural phenomenon;
Step (Revised 2A - Prong 2) do the claims recite additional elements that integrate the judicial exception into a practical application; and
Step (2B) whether the claim as a whole recites something that amounts to significantly more than the judicial exception. (See 2019 Revised Patent Subject Matter Eligibility Guidance (2019 PEG)).
Step 1: Yes; the claims are directed to a composition of matter.
Step 2A – Prong 1: Yes, the claims recite a natural phenomenon, namely, a naturally occurring product/protein.
Step 2A – Prong 2: No, the claims do not recite any additional elements that integrate the judicial exception into a practical application because the claims are merely drawn to what already exists in nature. As noted above, the claims are not limited in their ending sequence identity, only their beginning. As disclosed in the Supplemental Content, 20251214_143210_us-17-928-592-1.rup, Results #8 (from Thermus thermophilus), #9 (from Thermus brockianus), #13 (from Thermus thermophilus JL-18), and Result #45 substitutions compared to instant SEQ ID NO: 1 are found in the naturally occurring DNA polymerases resulting in differences of G499R/K, A501P, I503L, E507Q, as compared to SEQ ID NO: 1 for results 8, 9 and 13. Said sequences have ending identities of 88%, 87.9% and 87.5%, respectively, as compared to SEQ ID NO: 1 Taq DNA polymerase (See also citations and teachings below, and incorporated herein). Given the claims have the same structure, it is asserted that inherently the noted naturally occurring DNA polymerases will have the requisite maintained polymerization activity and also enhanced discrimination of an allelic or genetic mutation compared another wild-type DNA polymerase, such as Taq DNA polymerase (e.g. structure gives rise to function; and if the claimed structure is the same it must also have the claimed function, even if it is silent to this aspect). Thus, there is nothing in the claims which differentiates this naturally occurring enzyme in terms of structure and/or function. Thus, there is ultimately nothing in the claims which integrates the judicial exception into a practical application.
Step 2B: As noted in answering that of 2A – Prong 2 above, there is nothing in the claims which amounts to significantly more in terms of structure and/or function and the claims read on naturally occurring enzymes. Thus, the claims are drawn to a judicial exception, namely, a naturally occurring product.
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.
Claim(s) 1, 3, 9-10 and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yasukawa et al. (Biochem. Biophys. Res. Comm., 2012 – cited herein).
Yasukawa et al. teach a DNA polymerase from Thermus thermophilus having 88% sequence identity to Taq DNA polymerase of SEQ ID NO: 1 and having substitutions at positions: G499K, I503L and E507Q – See Supplemental Content, file 20251214_143210_us-17-928-592-1.rup, Result #8 (alignment reproduced herein).
With regard to the recited claimed function of maintained polymerization activity and also enhanced discrimination of an allelic or genetic mutation compared with a wild-type DNA polymerase, as noted in MPEP 2112.01(II), ““Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Query Match 88.0%; Score 3747; Length 834;
Best Local Similarity 87.6%;
Matches 730; Conservative 44; Mismatches 57; Indels 2; Gaps 2;
Qy 1 MRGMLPLFEPKGRVLLVDGHHLAYRTFHALKGLTTSRGEPVQAVYGFAKSLLKALKEDG- 59
| |||||||||||||||||||||||| |||||:|||||||||||||||||||||||||
Db 1 MEAMLPLFEPKGRVLLVDGHHLAYRTFFALKGLSTSRGEPVQAVYGFAKSLLKALKEDGY 60
Qy 60 DAVIVVFDAKAPSFRHEAYGGYKAGRAPTPEDFPRQLALIKELVDLLGLARLEVPGYEAD 119
|| ||||||||||||||| ||||||||||||||||||||||||||| ||||||||||
Db 61 KAVFVVFDAKAPSFRHEAYEAYKAGRAPTPEDFPRQLALIKELVDLLGFTRLEVPGYEAD 120
Qy 120 DVLASLAKKAEKEGYEVRILTADKDLYQLLSDRIHVLHPEGYLITPAWLWEKYGLRPDQW 179
||||:||||||||||||||||||:|||||:|||: ||||||:|||| ||||||||||:||
Db 121 DVLATLAKKAEKEGYEVRILTADRDLYQLVSDRVAVLHPEGHLITPEWLWEKYGLRPEQW 180
Qy 180 ADYRALTGDESDNLPGVKGIGEKTARKLLEEWGSLEALLKNLDRLKPA-IREKILAHMDD 238
|:||| || ||||||||||||||| |||:|||||| |||||||:|| :|||| ||::|
Db 181 VDFRALVGDPSDNLPGVKGIGEKTALKLLKEWGSLENLLKNLDRVKPENVREKIKAHLED 240
Qy 239 LKLSWDLAKVRTDLPLEVDFAKRREPDRERLRAFLERLEFGSLLHEFGLLESPKALEEAP 298
|:|| :|::|||||||||| |: |||||| |||||||||||||||||||||:| |||||
Db 241 LRLSLELSRVRTDLPLEVDLAQGREPDREGLRAFLERLEFGSLLHEFGLLEAPAPLEEAP 300
Qy 299 WPPPEGAFVGFVLSRKEPMWADLLALAAARGGRVHRAPEPYKALRDLKEARGLLAKDLSV 358
||||||||||||||| |||||:| |||| | |||||| :| |:|||| ||||||||:|
Db 301 WPPPEGAFVGFVLSRPEPMWAELKALAACRDGRVHRAADPLAGLKDLKEVRGLLAKDLAV 360
Qy 359 LALREGLGLPPGDDPMLLAYLLDPSNTTPEGVARRYGGEWTEEAGERAALSERLFANLWG 418
|| |||| | ||||||||||||||||||||||||||||||||:| || ||||| ||
Db 361 LASREGLDLVPGDDPMLLAYLLDPSNTTPEGVARRYGGEWTEDAAHRALLSERLHQNLLK 420
Qy 419 RLEGEERLLWLYREVERPLSAVLAHMEATGVRLDVAYLRALSLEVAEEIARLEAEVFRLA 478
||:|||:||||| |||:||| ||||||||||:||||||:|||||:|||| ||| ||||||
Db 421 RLQGEEKLLWLYHEVEKPLSRVLAHMEATGVQLDVAYLQALSLELAEEIRRLEEEVFRLA 480
Qy 479 GHPFNLNSRDQLERVLFDELGLPAIGKTEKTGKRSTSAAVLEALREAHPIVEKILQYREL 538
|||||||||||||||||||| |||:|||:|||||||||||||||||||||||||||:|||
Db 481 GHPFNLNSRDQLERVLFDELKLPALGKTQKTGKRSTSAAVLEALREAHPIVEKILQHREL 540
Qy 539 TKLKSTYIDPLPDLIHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAF 598
||||:||:|||| |:|||||||||||||||||||||||||||||||||||||||||||||
Db 541 TKLKNTYVDPLPSLVHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAF 600
Qy 599 IAEEGWLLVALDYSQIELRVLAHLSGDENLIRVFQEGRDIHTETASWMFGVPREAVDPLM 658
:|| || ||||||||||||||||||||||||||||||:||||:||||||||| |||||||
Db 601 VAEAGWALVALDYSQIELRVLAHLSGDENLIRVFQEGKDIHTQTASWMFGVPPEAVDPLM 660
Qy 659 RRAAKTINFGVLYGMSAHRLSQELAIPYEEAQAFIERYFQSFPKVRAWIEKTLEEGRRRG 718
||||||:|||||||||||||||||:|||||| |||||||||||||||||||||||||:||
Db 661 RRAAKTVNFGVLYGMSAHRLSQELSIPYEEASAFIERYFQSFPKVRAWIEKTLEEGRKRG 720
Qy 719 YVETLFGRRRYVPDLEARVKSVREAAERMAFNMPVQGTAADLMKLAMVKLFPRLEEMGAR 778
||||||||||||||| |||||||||||||||||||||||||||||||||||||| |||||
Db 721 YVETLFGRRRYVPDLNARVKSVREAAERMAFNMPVQGTAADLMKLAMVKLFPRLREMGAR 780
Qy 779 MLLQVHDELVLEAPKERAEAVARLAKEVMEGVYPLAVPLEVEVGIGEDWLSAK 831
|||||||||||||||:||: || ||||||||||||||||||||||||||||||
Db 781 MLLQVHDELVLEAPKDRAQEVAALAKEVMEGVYPLAVPLEVEVGIGEDWLSAK 833
Claim(s) 1, 3, 9-10 and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schafers et al. (Standards in Genomic Science, 2017 – cited herein).
Schafers et al. teach a DNA polymerase from Thermus brockianus having 87.9% sequence identity to Taq DNA polymerase of SEQ ID NO: 1 and having substitutions at positions: A502P – See Supplemental Content, file 20251214_143210_us-17-928-592-1.rup, Result #9 (alignment reproduced herein).
With regard to the recited claimed function of maintained polymerization activity and also enhanced discrimination of an allelic or genetic mutation compared with a wild-type DNA polymerase, as noted in MPEP 2112.01(II), ““Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Query Match 87.9%; Score 3742.5; Length 830;
Best Local Similarity 87.3%;
Matches 724; Conservative 52; Mismatches 52; Indels 1; Gaps 1;
Qy 4 MLPLFEPKGRVLLVDGHHLAYRTFHALKGLTTSRGEPVQAVYGFAKSLLKALKEDGDAVI 63
|||||||||||||||||||||| | |||||||||||||| ||||||||||||||||| ||
Db 1 MLPLFEPKGRVLLVDGHHLAYRNFFALKGLTTSRGEPVQGVYGFAKSLLKALKEDGDVVI 60
Qy 64 VVFDAKAPSFRHEAYGGYKAGRAPTPEDFPRQLALIKELVDLLGLARLEVPGYEADDVLA 123
|||||||||||||||| ||||||||||||||||||:||||||||| ||||||:|||||||
Db 61 VVFDAKAPSFRHEAYGAYKAGRAPTPEDFPRQLALMKELVDLLGLERLEVPGFEADDVLA 120
Qy 124 SLAKKAEKEGYEVRILTADKDLYQLLSDRIHVLHPEGYLITPAWLWEKYGLRPDQWADYR 183
:||||||:|||||||||||:||:||||||| ||||||:|||| ||||:|||||:|| |:|
Db 121 ALAKKAEREGYEVRILTADRDLFQLLSDRIAVLHPEGHLITPGWLWERYGLRPEQWVDFR 180
Qy 184 ALTGDESDNLPGVKGIGEKTARKLLEEWGSLEALLKNLDRLK-PAIREKILAHMDDLKLS 242
|| || |||:||||||||||| |||:|||||| : ||||:: |::|||| ||:|||:||
Db 181 ALAGDPSDNIPGVKGIGEKTALKLLKEWGSLENIQKNLDQVSPPSVREKIQAHLDDLRLS 240
Qy 243 WDLAKVRTDLPLEVDFAKRREPDRERLRAFLERLEFGSLLHEFGLLESPKALEEAPWPPP 302
:|::||||||||||| :||||||| |||||||||||||||||||||||:| ||||||||
Db 241 QELSRVRTDLPLEVDFRRRREPDREGLRAFLERLEFGSLLHEFGLLESPQAAEEAPWPPP 300
Qy 303 EGAFVGFVLSRKEPMWADLLALAAARGGRVHRAPEPYKALRDLKEARGLLAKDLSVLALR 362
||||:|| ||| |||||:||:|||: |||:|| |:||| |||| ||||||||:|||||
Db 301 EGAFLGFRLSRPEPMWAELLSLAASAKGRVYRAEAPHKALSDLKEIRGLLAKDLAVLALR 360
Qy 363 EGLGLPPGDDPMLLAYLLDPSNTTPEGVARRYGGEWTEEAGERAALSERLFANLWGRLEG 422
||||||| |||||||||||||||||||||||||||||||||||| |:|||: || ||:|
Db 361 EGLGLPPTDDPMLLAYLLDPSNTTPEGVARRYGGEWTEEAGERALLAERLYENLLSRLKG 420
Qy 423 EERLLWLYREVERPLSAVLAHMEATGVRLDVAYLRALSLEVAEEIARLEAEVFRLAGHPF 482
||:||||| |||:||| |||||||||||||| |||||||||| |: ||| ||||||||||
Db 421 EEKLLWLYEEVEKPLSRVLAHMEATGVRLDVPYLRALSLEVAAEMGRLEEEVFRLAGHPF 480
Qy 483 NLNSRDQLERVLFDELGLPAIGKTEKTGKRSTSAAVLEALREAHPIVEKILQYRELTKLK 542
||||||||||||||||||| |||||||||||||||||||||||||||||||||||| |||
Db 481 NLNSRDQLERVLFDELGLPPIGKTEKTGKRSTSAAVLEALREAHPIVEKILQYRELAKLK 540
Qy 543 STYIDPLPDLIHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAFIAEE 602
||||||| |:|||||||||||||||||||||||||||||||||||||||||||||:|||
Db 541 GTYIDPLPALVHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAFVAEE 600
Qy 603 GWLLVALDYSQIELRVLAHLSGDENLIRVFQEGRDIHTETASWMFGVPREAVDPLMRRAA 662
|:||||||||||||||||||||||||||||||||||||:|||||||:| ||:||| ||||
Db 601 GYLLVALDYSQIELRVLAHLSGDENLIRVFQEGRDIHTQTASWMFGLPAEAIDPLRRRAA 660
Qy 663 KTINFGVLYGMSAHRLSQELAIPYEEAQAFIERYFQSFPKVRAWIEKTLEEGRRRGYVET 722
|||||||||||||||||||| |||||| |||:|||||:|||:||||:||||||:||||||
Db 661 KTINFGVLYGMSAHRLSQELGIPYEEAVAFIDRYFQSYPKVKAWIERTLEEGRQRGYVET 720
Qy 723 LFGRRRYVPDLEARVKSVREAAERMAFNMPVQGTAADLMKLAMVKLFPRLEEMGARMLLQ 782
||||||||||| ||||||||||||||||||||||||||||||||:||||| |:|||||||
Db 721 LFGRRRYVPDLNARVKSVREAAERMAFNMPVQGTAADLMKLAMVRLFPRLPEVGARMLLQ 780
Qy 783 VHDELVLEAPKERAEAVARLAKEVMEGVYPLAVPLEVEVGIGEDWLSAK 831
|||||:||||||||| | |||||||||:||||||||||||||||||||
Db 781 VHDELLLEAPKERAEEAAALAKEVMEGVWPLAVPLEVEVGIGEDWLSAK 829
Claim(s) 1, 3, 9-10 and 14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Asakura et al. (J. Ferment. Bioeng., 1993 – cited herein).
Asakura et al. teach a DNA polymerase from Thermus thermophilus having 87.5% sequence identity to Taq DNA polymerase of SEQ ID NO: 1 and having substitutions at positions: G499R, I503L and E507Q – See Supplemental Content, file 20251214_143210_us-17-928-592-1.rup, Result #13 (alignment reproduced herein).
With regard to the recited claimed function of maintained polymerization activity and also enhanced discrimination of an allelic or genetic mutation compared with a wild-type DNA polymerase, as noted in MPEP 2112.01(II), ““Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Query Match 87.6%; Score 3733; Length 834;
Best Local Similarity 87.5%;
Matches 729; Conservative 41; Mismatches 61; Indels 2; Gaps 2;
Qy 1 MRGMLPLFEPKGRVLLVDGHHLAYRTFHALKGLTTSRGEPVQAVYGFAKSLLKALKEDG- 59
| |||||||||||||||||||||||| |||||||||||||||||||||||||||||||
Db 1 MEAMLPLFEPKGRVLLVDGHHLAYRTFFALKGLTTSRGEPVQAVYGFAKSLLKALKEDGY 60
Qy 60 DAVIVVFDAKAPSFRHEAYGGYKAGRAPTPEDFPRQLALIKELVDLLGLARLEVPGYEAD 119
|| ||||||||||||||| ||||||||||||||||||||||||||| ||||||||||
Db 61 KAVFVVFDAKAPSFRHEAYEAYKAGRAPTPEDFPRQLALIKELVDLLGFTRLEVPGYEAD 120
Qy 120 DVLASLAKKAEKEGYEVRILTADKDLYQLLSDRIHVLHPEGYLITPAWLWEKYGLRPDQW 179
||||:||||||||||||||||||:|||||:|||: ||||||:|||| ||||||||||:||
Db 121 DVLATLAKKAEKEGYEVRILTADRDLYQLVSDRVAVLHPEGHLITPEWLWEKYGLRPEQW 180
Qy 180 ADYRALTGDESDNLPGVKGIGEKTARKLLEEWGSLEALLKNLDRLKPA-IREKILAHMDD 238
|:||| || ||||||||||||||| |||:|||||| |||||||:|| :|||| ||::|
Db 181 VDFRALVGDPSDNLPGVKGIGEKTALKLLKEWGSLENLLKNLDRVKPENVREKIKAHLED 240
Qy 239 LKLSWDLAKVRTDLPLEVDFAKRREPDRERLRAFLERLEFGSLLHEFGLLESPKALEEAP 298
|:|| :|::|||||||||| |: |||||| |||||||||||||||||||||:| |||||
Db 241 LRLSLELSRVRTDLPLEVDLAQGREPDREGLRAFLERLEFGSLLHEFGLLEAPAPLEEAP 300
Qy 299 WPPPEGAFVGFVLSRKEPMWADLLALAAARGGRVHRAPEPYKALRDLKEARGLLAKDLSV 358
||||||||||||||| |||||:| |||| | |||||| :| |:|||| ||||||||:|
Db 301 WPPPEGAFVGFVLSRPEPMWAELKALAACRDGRVHRAADPLAGLKDLKEVRGLLAKDLAV 360
Qy 359 LALREGLGLPPGDDPMLLAYLLDPSNTTPEGVARRYGGEWTEEAGERAALSERLFANLWG 418
|| |||| | ||||||||||||||||||||||||||||||||:| || ||||| ||
Db 361 LASREGLDLVPGDDPMLLAYLLDPSNTTPEGVARRYGGEWTEDAAHRALLSERLHRNLLK 420
Qy 419 RLEGEERLLWLYREVERPLSAVLAHMEATGVRLDVAYLRALSLEVAEEIARLEAEVFRLA 478
||||||:||||| |||:||| |||||||||||||||||:|||||:|||| ||| ||||||
Db 421 RLEGEEKLLWLYHEVEKPLSRVLAHMEATGVRLDVAYLQALSLELAEEIRRLEEEVFRLA 480
Qy 479 GHPFNLNSRDQLERVLFDELGLPAIGKTEKTGKRSTSAAVLEALREAHPIVEKILQYREL 538
|||||||||||||||||||| |||:|||:|||||||||||||||||||||||||||:|||
Db 481 GHPFNLNSRDQLERVLFDELRLPALGKTQKTGKRSTSAAVLEALREAHPIVEKILQHREL 540
Qy 539 TKLKSTYIDPLPDLIHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAF 598
||||:||:|||| |:|||||||||||||||||||||||||||||||||||||||||||||
Db 541 TKLKNTYVDPLPSLVHPRTGRLHTRFNQTATATGRLSSSDPNLQNIPVRTPLGQRIRRAF 600
Qy 599 IAEEGWLLVALDYSQIELRVLAHLSGDENLIRVFQEGRDIHTETASWMFGVPREAVDPLM 658
:|| || ||||||||||||||||||||||||||||||:||||:||||||||| |||||||
Db 601 VAEAGWALVALDYSQIELRVLAHLSGDENLIRVFQEGKDIHTQTASWMFGVPPEAVDPLM 660
Qy 659 RRAAKTINFGVLYGMSAHRLSQELAIPYEEAQAFIERYFQSFPKVRAWIEKTLEEGRRRG 718
||||||:|||||||||||||||||||||||| |||||||||||||||||||||||||:||
Db 661 RRAAKTVNFGVLYGMSAHRLSQELAIPYEEAVAFIERYFQSFPKVRAWIEKTLEEGRKRG 720
Qy 719 YVETLFGRRRYVPDLEARVKSVREAAERMAFNMPVQGTAADLMKLAMVKLFPRLEEMGAR 778
||||||||||||||| |||||||||||||||||||||||||||||||||||||| |||||
Db 721 YVETLFGRRRYVPDLNARVKSVREAAERMAFNMPVQGTAADLMKLAMVKLFPRLREMGAR 780
Qy 779 MLLQVHDELVLEAPKERAEAVARLAKEVMEGVYPLAVPLEVEVGIGEDWLSAK 831
|||||||||:||||: ||| || |||| || ||||||||||||:||||||||
Db 781 MLLQVHDELLLEAPQARAEEVAALAKEAMEKAYPLAVPLEVEVGMGEDWLSAK 833
Claim(s) 1, 3-5, 10 and 13-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Skirgaila et al. (US 20130034879 – cited on IDS).
Given the ambiguity of the noted substitutions in positions 507 (See 112(b) rejection above), the instant rejection is applied.
Skirgaila et al. et al. teach mutations/substitutions made to wild-type Taq DNA polymerase comprising SEQ ID NO: 13 (Figure 1), which has 100% sequence identity to instant SEQ ID NO: 1 – See Supplemental Content, 20251214_143210_us-17-928-592-1.rapbm file, Duplicates for Result #1, wherein said substitutions are selected from those inclusive of G504S and E507A/K – See claims 1 and 6. Said mutants are utilized in RT-PCR reactions – See Example 2. Although these claims recite several alternative substitutions which could be utilized, one of ordinary skill would have immediately envisaged each of said alternatives and thus the disclosure of Skirgaila et al. is taken as anticipatory over the claimed invention.
With regard to the recited claimed function of maintained polymerization activity and also enhanced discrimination of an allelic or genetic mutation compared with a wild-type DNA polymerase, as noted in MPEP 2112.01(II), ““Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Given the ambiguity as noted in the 112(b) rejection above regarding whether or not positions 507 and 508 are to be included in claim 1 and the interpretation that they inadvertently were not included in claim 1, then the instant rejection applies.
Claim(s) 1, 3-5, 9-10 and 13-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schafer et al. (US 9315787 – cited on IDS).
Given the ambiguity of the noted substitutions in positions 507 (See 112(b) rejection above), the instant rejection is applied.
Schafer et al. teach mutations/substitutions made to wild-type Taq DNA comprising SEQ ID NO: 1 or SEQ ID NO: 38, which has 100% sequence identity to instant SEQ ID NO: 1 (See Supplemental Content, 20251214_143210_us-17-928-592-1.rai, Duplicates for Result #1), which has substitutions in at least two positions selected from A61, K346, S357, E507 and I707 – See claims 1 and 3.
Claim(s) 1, 3-5 and 13-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mazur et al. (US 9976178 – cited on IDS).
Mazur et al. teach mutations/substitutions made to wild-type Taq DNA comprising SEQ ID NO: 1 which has 100% sequence identity to instant SEQ ID NO: 1 (See Supplemental Content, 20251214_143210_us-17-928-592-1.rai, Duplicates for Result #1), which has substitutions in at least one position selected from P6N, A77E, A97V, L193V, K240I, R266Q, E267T, L287T, P291T, K292C, E295F or E295N, E397V, G418C, L490Q, A502S, S543V, D578E, R593G, L678F or L678T, S699W, E713W, V737A, E745T, L763F, E790G, E794C, E805I and L828 – See Col. 3, lines 42-62.
Although this passage recites several alternative substitutions which could be utilized, one of ordinary skill would have immediately envisaged each of said alternatives and thus the disclosure of Mazur et al. is taken as anticipatory over the claimed invention.
With regard to the recited claimed function of maintained polymerization activity and also enhanced discrimination of an allelic or genetic mutation compared with a wild-type DNA polymerase, as noted in MPEP 2112.01(II), ““Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Claim(s) 1, 3-5, 9-10 and 13-14 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hogrefe et al. (US 20110027833 – cited herein).
Hogrefe et al. teach:
Regarding claims 1, 3-5, 10, 14 a variant Taq DNA polymerase having a first substitution at E507, specifically, E507K and an additional substitution selected from position including K508 (See claim 1). The variant Taq DNA polymerase comprises substitutions: G59W, L245M, L375V, E507K, K508R, E734G, and F749I (See claims 1, 6-7). Said substitutions give rise to increased rates of incorporation of nucleotides undergoing polymerization and enhanced resistance to inhibitors of DNA polymerase activity. The Taq DNA polymerase that is used to introduce the substitutions is SEQ ID NO: 4, which has 100% sequence identity to instant SEQ ID NO: 1 – See Supplemental Content, 20251214_143210_us-17-928-592-1.rapbm file, Duplicates for Result #1; and see paragraph 0037.
Regarding claim 13, said variant polymerases were utilized for RT-PCR – See Examples.
With regard to the recited claimed function of maintained polymerization activity and also enhanced discrimination of an allelic or genetic mutation compared with a wild-type DNA polymerase, as noted in MPEP 2112.01(II), ““Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.”
Given the ambiguity as noted in the 112(b) rejection above regarding whether or not positions 507 and 508 are to be included in claim 1 and the interpretation that they inadvertently were not included in claim 1, then the instant rejection applies.
Conclusion
No claim is allowed.
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 18 December 2025