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 .
Status of Claims
Applicant’s amendment filed 06/28/2023 is acknowledged. Claims 1, 3-5, and 7-13 have been amended. Claim 15 has been added. Claims 1-15 are pending in the instant application and the subject of this non-final office action.
Specification
The use of the terms including but not limited to “SYBR Green” and “EvaGreen”, each which is a trade name or a mark used in commerce, has been noted in this application. The such terms should be accompanied by the generic terminology; furthermore such terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 9 is objected to because of the following informalities: The claim recites “primary- or modified cells and/or tissues“. The hyphen after “primary” appears to be a typo. Appropriate correction is required.
Claim Interpretation
In evaluating the patentability of the claims presented in this application, claim terms have been given their broadest reasonable interpretation (BRI) consistent with the specification, as understood by one of ordinary skill in the art, as outlined in MPEP 2111.
Regarding claim 1, it is noted that the steps of adding a strand-displacing polymerase followed by addition of at least five primers and at least one step of incubating at a fixed temperature before determining the presence of an elongated DNA sequence read on a variety of multiplexed amplification techniques, including multiplex PCR that utilizes a strand displacement polymerase (see Prior Art at conclusion, for example), in addition to single-plex techniques that require five or more primers, such as LAMP.
It is noted that step (d) requires determining whether a “double-stranded elongated DNA sequence” is present and that step (a) requires RNA- and/or DNA-dependent DNA-polymerase activity. For a double-stranded DNA molecule comprising a double-stranded DNA sequence indicative of the pre-determined nucleic acid sequence to be present, it is noted that a DNA-dependent DNA polymerase would be required in step (a) or a subsequence undisclosed step.
Regarding claims 1 and 12, the claims recite the “double-stranded DNA sequence”. The term was interpreted broadly to encompass DNA molecules or sequences of molecules including those have undergone via a replication reaction, i.e., elongation (instant specification, pg. 4, para 2: “e.g., via an enzymatic nucleic acid replication reaction”) and those that have otherwise undergone a “lengthening”.
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.
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 12-13 and 15 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.
Regarding claims 12 and 15, the claims recite “wherein presence of the double-stranded elongated DNA sequence in the sample is determined by using a nucleic acid molecule hybridisable to the double-stranded elongated DNA sequence” (claim 12) “wherein the nucleic acid molecule is labelled, using a molecule that intercalates in the double-stranded elongated DNA sequence or using turbidity measurement.” (claim 15)
First, the claim appears to require “a nucleic acid molecule” capable of hybridizing to a double-stranded elongated DNA molecule. However, the embodiments of claim 15 seem inconsistent with such an interpretation.
The specification defines “intercalates” as “an agent or moiety capable of non-covalent insertion between stacked base pairs in a nucleic acid double helix” (pg. 16, para 2; emphasis added). It is not clear how a nucleic acid hybridizable to a double-stranded sequence (i.e., forming triplex DNA?) is compatible with the embodiment of claim 15 of an intercalating agent. Likewise for turbidity, the specification describes, for example, the embodiment in which pyrophosphate ions released during polymerization result in an insoluble magnesium pyrophosphate precipitate (pg. 17, para 1), wherein no additional probe or similar molecule is present.
For these reasons, claim 12 has been interpreted, for the purposes of applying art, that the nucleic acid molecule hybridizable to the double-stranded elongated DNA sequence may originate from the elongation [e.g., be one strand of the double-stranded elongated DNA sequence] or my hybridize to either strand of the double-stranded DNA sequence.
Regarding claim 13, the claim recites “an efficient amount of an antibiotic”. The term “efficient” is a relative term which renders the claim indefinite. The term “efficient” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
The specification defines “most efficient” in pg. 6, para 2; however, the definition is only in the context of detection. It is unclear what is meant by efficient in this context (financial efficiency, time efficiency, minimal cell death efficiency, etc.). Therefore, the metes and bounds would not be clear to one ordinary skill in the art.
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 1-13 and 15 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more. The claim(s) recite(s) an abstract idea. This judicial exception is not integrated into a practical application The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
The following three inquiries are used to determine whether a claim is drawn to patent-eligible subject matter:
Step 1. Is the claim to a process, machine, manufacture, or composition of matter?
Yes, the claims are directed to a process.
Step 2A, prong 1. Does the claim recite a law of nature, a natural phenomenon, or an abstract idea (recognized judicial exceptions)?
The claims recite determining whether an elongated DNA sequence is present in the sample, wherein the presence of the elongated DNA sequence in the sample is indicative of the pre-determined nucleic acid sequence in the sample (as recited in claim 1). The claims are thus directed to the abstract idea of a mental process (observations, evaluations, or judgements of visual input, data, or information to render a judgement or opinion). See MPEP 2106.04(a).
Step 2A, prong 2. Are the judicial are integrated into a practical application?
Regarding claims 1-12 and 15, the judicial exception is not integrated into a practical application because the claims do not include additional elements that amount to significantly more than well understood, routine and conventional steps in the art, wherein such are utilized for data gathering for the step (d) that encompasses a mental process.
It is noted that Lobato (Lobato IM, O'Sullivan CK. Recombinase polymerase amplification: Basics, applications and recent advances. Trends Analyt Chem. 2018 Jan;98:19-35.) teaches that strand-displacing polymerases and multiplexing are well known among isothermal techniques (pg. 19, 2.1. RPA mechanism, para 1, spanning pg. 20; pg. 19, Introduction, para 1; Table 1; see also Tables 2-6 for targets and samples).
Elnifro (Elnifro EM, et al. Multiplex PCR: optimization and application in diagnostic virology. Clin Microbiol Rev. 2000 Oct;13(4):559-70) likewise teaches that set of at least 5 primers for amplification are well known within the art (pg. 563, col 2, para 2; pg. 567, col 2, para 1).
It is further noted that the particular pathogen and the sample merely directs the selection of the data for the previously discussed data gathering methods.
Therefore, the claims are directed to the abstract idea.
Regarding claims 13, the claims recite a method for treatment using the method of claim 1. As is discussed in MPEP 2106.04(d)(2), effecting a particular treatment demonstrates integration into a practical application. Administering an efficient dose of a generically recited antibiotic to treat a bacterium of the Mollicutes class is not particular. The bacteria lack a cell wall and therefore only a subset of antibiotics are known to be effective, as taught by Chernova (Chernova OA, et al. Mycoplasmas and Their Antibiotic Resistance: The Problems and Prospects in Controlling Infections. Acta Naturae. 2016 Apr-Jun;8(2):24-34.; pg. 25 col 1, para 1).
Thus, the claims, in addition to the reasons discussed for 1-12 and 15, this claim is not integrated into a practical application under Step 2A Prong Two and remain directed at the judicial exception.
Step 2B. Does the claim amount to significantly more?
Regarding claims 1-13 and 15, the claims do not include addition element that are sufficient to amount to significantly more than the judicial exception because the practical steps of the claims are well understood, routine, and convention in the related art, as cited in Step 2A Prong Two. In the instant case, the additional elements are data gathering steps. Application to particular pathogens and samples represents a selection of specific data. The treatment step discussed above in the method comprising treatment is not particular. Therefore, these claims include no additional elements sufficient to represent significantly more.
Claim Rejections - 35 USC § 103
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Georgiou (WO 2019/234251 A1; published 12/12/2019) in view of Uphoff (Uphoff CC, et al. Treatment of mycoplasma contamination in cell cultures with Plasmocin. J Biomed Biotechnol. 2012;2012:267678. Epub 2012 Oct 2.) as evidenced by Tanner (New England Biolabs, Inc. Isothermal Amplification [Internet]. Ipswich (MA): New England Biolabs, Inc.; 2015 Apr [cited 2025 Aug 26]. Available from: https://www.neb-online.de/wp-content/uploads/2015/04/NEB_isothermal_amp.pdf) and Hopert (Hopert A, et al. Specificity and sensitivity of polymerase chain reaction (PCR) in comparison with other methods for the detection of mycoplasma contamination in cell lines. J Immunol Methods. 1993 Aug 26;164(1):91-100)
Regarding claims 1 and 4-8, Georgiou teaches a method for determining presence of a pre-determined nucleic acid sequence in a sample (pg. 47), the method comprising the steps of:
(a) adding an enzyme to the sample to be analysed for the presence of the pre-determined nucleic acid sequence (pg. 47, lines 5-8), wherein the enzymes provide activities of RNA- and/or DNA-dependent DNA polymerase activity and strand-displacement activity (pg. 9, para 5-6; pg. 2, para 9);
(b) adding at least five DNA primers to the sample to be analysed for the presence of the pre-determined nucleic acid sequence, wherein at least one DNA primer comprises a sequence hybridisable to the nucleic acid sequence and at least one DNA primer comprises a sequence hybridisable to the DNA sequence reverse-complementary to the nucleic acid sequence (pg. 47: (iv): FIP, (v): BIP, (vi): forward blocking, (vii): backward blocking; pg. 23, lines 10-11: forward loop primer and backward loop primer; pg. 22, lines 22-23; pg. 22, lines 36-37)
(c) incubating the sample resulting from steps (a) and (b) at a fixed temperature (pg. 47, (a): “amplifying under isothermal conditions” [i.e., a fixed temperature]);
(d) determining whether an elongated DNA sequence is present in the sample, wherein presence of the elongated DNA sequence in the sample is indicative of the presence of the pre-determined nucleic acid sequence in the sample (pg. 47, (b))
Georgiou teaches a polymerase with strand-displacement activity at least by teaching that the DNA polymerase when the nucleic acid sequence is DNA (instant claim 4 and 8) may be Bst 2.0 DNA polymerase (pg. 9, para 5), evidenced by Tanner. While Georgiou does not explicitly teach that the polymerase itself has strand-displacement activity, it is inherently taught because Bst 2.0 has strand-displacement activity, evidenced by Tanner (pg. 4, para 1: “Bst 2.0 DNA polymerase possesses … strong strand-displacement activity”).
Georgiou teaches that if the nucleic acid sequence if RNA, the method may also comprise reverse transcription of the RNA to produce cDNA (pg. 9, lines 36-40; instant claims 4 and 7).
Georgiou teaches an embodiment without F3 (pg. 22, lines 22-23: “The reaction mixture may further comprise … F3 … and/or … B3 …” (emphasis added); pg. 22, lines 36-37: “The present inventors have determined that detectable amplification of the nucleic acid can occur in the absence of F3 and/or B3”). Georgiou teaches [traditional] LAMP uses four to six primers in the reaction (pg. 2, line 9), and that the efficiency of the reaction is enhanced by the addition of B3 (pg. 23, lines 6-7) and LF and LB (pg. 23, line 22).
Georgiou does not teach that the pre-determined nucleic acid sequence is from a bacterium of the Mollicutes class.
Uphoff rectifies this by teaching that cell culture has become an important research tool, wherein one of the major problems of the cell culture field is infection with mycoplasma, which can affect every cellular parameter, often leading to experimental artefacts and spurious results (pg. 1, Introduction, para 1).
Uphoff teaches verification of mycoplasma contamination by targeting the 16S rRNA gene of bacteria including M. arginini [i.e., Mycoplasma arginini], M. fermentas, A. laidlawii [i.e., Acholeplasma laidlawii], M. pneumoniae, and M. orale (instant claims 5-6), evidenced by Hopert. While Uphoff does not explicitly teach targeting the 16S rRNA of those bacteria species, it is inherently taught because Uphoff utilizes the methods of Hopert (Uphoff : pg. 2, 2.2. Mycoplasma Detection and Species Identification by PCR, para 1; Uphoff : Table 1), as evidenced by Hopert (Hopert: Abstract; Table 1).
Uphoff teaches that the advent of specific antimycoplasma antibiotics together with the availability of the most sensitive and robust detection method represent efficient methods to achieve mycoplasma-free cultures (pg. 6, Discussion, para 1), wherein it is mandatory to document the [treatment] outcome with sensitive assays in order to verify complete and permanent freedom from mycoplasma (pg. 7, col 2, para 2).
Therefore, it would have been obvious to one of ordinary skill in the art at the time of filing to utilize the 16S rRNA gene of the above Mollicutes species as a target, as taught by Uphoff as evidenced by Hopert, in the method of Georgiou as evidenced by Tanner utilizing either RNA or DNA as a target nucleic acid, motivated by the desire enable verification of both the infection of cell cultures and the successful treatment to address the problematic infection of research cell cultures, as taught by Uphoff as evidenced by Hopert. There would have been a strong expectation for success as both are directed to identifying and treating infectious bacteria using amplification means, wherein one represents the application of a known technique to a known method.
It further would have been oblivious to add LF [instant LPF] and LB [instant LPB] and/or B3 in the method of determining the presence of a sequence in a sample Georgiou evidenced by Tanner, motivated by the desire to increase the efficiency the reaction, as taught by Georgiou.
There would be a strong expectation for success as the methods fall within the scope of Georgiou and are a combination of prior are elements according to known methods to yield predictable results.
Further, while Georgiou teaches embodiments with FIP, BIP, FB, BB, LF, LB, and L3 (at least 5 primers), the total number of primers utilized represents a matter for efficiency/optimization, as taught by Georgiou (e.g., typical number of LAMP primers, addition of LB and LF and/or L3).
It is noted that the courts have found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Thus, the claimed range of the number of primers merely represents routine optimization of the values of the cited prior art.
Applicant is advised that MPEP 716.01(c) makes clear that “[t]he arguments of counsel cannot take the place of evidence in the record” (In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965)). Thus, Applicant should not merely rely upon counsel's arguments in place of evidence in the record.
Regarding claim 2, in the method of Georgiou in view of Uphoff as evidenced by Tanner and Hopert, as cited in the rejection of claim 1, Georgiou teaches primers including FIP and BIP in the method and an embodiment in which LF [instant LPF] and LB [LPB] are added to improve efficiency. The same motivations and expectations for success as above apply.
Regarding claim 3, in the method of Georgiou in view of Uphoff as evidenced by Tanner and Hopert, as cited in the rejection of claim 1, Georgiou teaches a method with FIP, BIP, and forward and backward blocking primers and an embodiment in which B3 is added to improve efficiency. The same motivations and expectations for success as above apply. The matter of B3 being “the fifth primer” is mere nomenclature and any of the primers, including B3, may be considered “the fifth primer”.
Regarding claim 9, in the method of Georgiou in view of Uphoff as evidenced by Tanner and Hopert, Uphoff teaches sampling cell cultures (pg. 2, 2.2. Mycoplasma Detection and Species Identification by PCR, para 1).
Regarding claim 10, in the method of Georgiou in view of Uphoff as evidenced by Tanner and Hopert, Georgiou teaches that the temperature for the isothermal conditions may be around 50 to 70 C (pg. 6, line 8).
Regarding claim 11, in the method of Georgiou in view of Uphoff as evidenced by Tanner and Hopert, Georgiou teaches the amplifying duration may be around 1 to 150 minutes and ranges in between (pg. 6, para 2).
Regarding claims 12 and 15, in the method of Georgiou in view of Uphoff as evidenced by Tanner and Hopert, Georgiou teaches detection of amplification products [i.e., double-stranded elongated DNA sequences/molecules] by turbidity and nucleic acid intercalating agents (pg. 7, lines 7-8).
Regarding claims 13 and 14, in the method of Georgiou in view of Uphoff as evidenced by Tanner and Hopert, Uphoff further teaches decontaminating a cell culture infected by a bacterium of the Mollicutes class by administering to the culture antimycoplasma antibiotic treatment protocols including BM-Cyclin (pg. 3, 2.3. Antimycoplasma Treatment and 2.4. Antimycoplasma Antibiotics).
Uphoff teaches that BM-Cyclin had the lowest resistance rate and highest cure rate of the three primary classes tested (Fig. 2).
Therefore, it further would have been obvious to one of ordinary skill in the art at the time of filing to treat the cultures identified as infected in the method of Georgiou in view of Uphoff as evidenced by Tanner and Hopert with an antimyoplasma antibiotic, motivated by the desire to address the problematic infection of research cell cultures, as taught by Uphoff . It further would have been obvious to choose BM-Cyclin, motivated by the low resistance rate and high cure rates identified. There would have been a strong expectation for success as the methods are directed to identifying and treating infectious bacteria using amplification means wherein such an improvement represents the application of a known technique to a known method.
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 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 and 8-10 of copending Application No. 18/009,498 in view of Uphoff (Uphoff CC, et al. Treatment of mycoplasma contamination in cell cultures with Plasmocin. J Biomed Biotechnol. 2012;2012:267678. Epub 2012 Oct 2.) as evidenced by Hopert (Hopert A, et al. Specificity and sensitivity of polymerase chain reaction (PCR) in comparison with other methods for the detection of mycoplasma contamination in cell lines. J Immunol Methods. 1993 Aug 26;164(1):91-100). This is a provisional nonstatutory double patenting rejection.
Both sets of claims are claims are directed to a method of determining a presence of a pre-determined nucleic acid sequence in a sample comprising the steps of adding an RNA/DNA-dependent DNA polymerase with strand-displacement activity and at least five primers, incubating at a fixed sample, and determining whether an elongated DNA sequence is present in the sample, wherein the elongated DNA sequence is indicative of the pre-determined sequence in the sample and wherein no F3 primer is used.
‘498 claim 6 teaches that the pathogen may be a bacterium.
Any additional limitations of the ‘498 claims are encompassed by the open claim language “comprising” found in the instant claims.
‘498 fails to teach specific species/genera of the Mollicutes class, a 16S or 23S gene target, a sample from cell culture or similar, or decontaminating an infected cell/tissue culture with an antibiotic including BM Cyclin.
Uphoff, as evidenced by Hopert, rectifies this. The teachings of Uphoff, as evidenced by Hopert, from the rejections of instant claim 1, 6-9, and 13-14 above are incorporated from above.
Uphoff further teaches that the cell lines of the method encompass animal cell lines from various tissue/cell types [i.e., were originally obtained from animal subjects] (Table 2). It is noted that the method of ‘498 requires that the sample be obtained from the animal subject and that the method states that is “comprising” the steps listed. Therefore, it has been interpreted to encompass the establishment of a cell culture from the animal sample.
It would have been obvious to combine ‘498 with the 16S method of identifying the Mollicutes species and treating with BM Cyclin of Uphoff as evidenced by Hopert, motivated by the desire enable verification of both the infection of cell cultures and the successful treatment to address the problematic infection of research cell cultures, especially with the low resistance rate/high cure rate of BM Cyclin, as taught by Uphoff . There would have been a strong expectation for success as the methods are directed to identifying and treating infectious bacteria using amplification means wherein such an improvement represents the application of a known technique to a known method.
Claims 1-14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-10 of copending Application No. 18/009,142 in view of Uphoff (Uphoff CC, et al. Treatment of mycoplasma contamination in cell cultures with Plasmocin. J Biomed Biotechnol. 2012;2012:267678. Epub 2012 Oct 2.) as evidenced by Hopert (Hopert A, et al. Specificity and sensitivity of polymerase chain reaction (PCR) in comparison with other methods for the detection of mycoplasma contamination in cell lines. J Immunol Methods. 1993 Aug 26;164(1):91-100). This is a provisional nonstatutory double patenting rejection.
Both sets of claims are claims are directed to a method of determining a presence of a pre-determined nucleic acid sequence in a sample comprising the steps of adding an RNA/DNA-dependent DNA polymerase with strand-displacement activity and at least five primers, incubating at a fixed sample, and determining whether an elongated DNA sequence is present in the sample, wherein the elongated DNA sequence is indicative of the pre-determined sequence in the sample and wherein no F3 primer is used.
‘142 claim 7 teaches that the pathogen may be from the genus Mycoplasma, which is part of the Mollicutes class, as evidenced by instant claim 5.
Any additional limitations of the ‘142 claims are encompassed by the open claim language “comprising” found in the instant claims.
‘142 fails to teach specific species of the Mollicutes class, a 16S or 23S gene target, a sample from cell culture or similar, or decontaminating an infected cell/tissue culture with an antibiotic including BM Cyclin.
Uphoff, as evidenced by Hopert, rectifies this. The teachings of Uphoff, as evidenced by Hopert, from the rejections of instant claim 1, 6-9, and 13-14 are incorporated from the rejections above.
Uphoff further teaches that the cell lines of the method encompass human cell lines from various tissue/cell types [i.e., were originally obtained from human subjects] (Table 2). It is noted that the method of ‘142 requires that the sample be obtained from the human subject and that the method states that is “comprising” the steps listed. Therefore, it has been interpreted to encompass the establishment of a cell culture from the human sample.
It would have been obvious to combine ‘142 with the 16S method of identifying the Mollicutes species and treating with BM Cyclin of Uphoff as evidenced by Hopert, motivated by the desire enable verification of both the infection of cell cultures and the successful treatment to address the problematic infection of research cell cultures, especially with the low resistance rate/high cure rate of BM Cyclin, as taught by Uphoff . There would have been a strong expectation for success as the methods are directed to identifying and treating infectious bacteria using amplification means wherein such an improvement represents the application of a known technique to a known method.
Additional Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Ignatov (Ignatov KB, et al. A strong strand displacement activity of thermostable DNA polymerase markedly improves the results of DNA amplification. Biotechniques. 2014 Aug 1;57(2):81-7.) teaches a DNA-dependent DNA polymerase with uses in PCR, LAMP, and PCDR applications, wherein the strand displacement activity of said polymerase provided a notable improvement in sensitivity and efficacy of all the methods (Abstract).
Nummi (Nummi M, et al. Development of a multiplex real-time PCR assay for detection of Mycoplasma pneumoniae, Chlamydia pneumoniae and mutations associated with macrolide resistance in Mycoplasma pneumoniae from respiratory clinical specimens. Springerplus. 2015 Nov 10;4:684.) teaches a quadraplex [i.e., eight primer] PCR assay targeting the 23S rRNA gene of M. pneumoniae (Abstract). The amplification comprises 60 C for 1 min (pg. 5, Multiplex real-time PCR design, para 1).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMMA R HOPPE whose telephone number is (703)756-5550. The examiner can normally be reached Mon - Fri 11:00 am - 7:00 pm.
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/EMMA R HOPPE/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
Prosecution Insights