DETAILED CORRESPONDENCE
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 .
This action is in response to the papers filed November 12, 2024. Currently, claims 1-20 are pending.
Priority
This application is a 371 of PCT/PL2022/050044, filed July 7, 2022 and claims priority to POLAN P.438373, filed July 7, 2021.
Drawings
The drawings are acceptable.
Claim Rejections - 35 USC § 112
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.
Claim 7 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 7 is directed to the set of primers as defined in Claim 1 and then has SEQ ID NO: 1 in parentheses. It is unclear whether Claim 7 encompasses 90% identify to SEQ ID NO: 1 or Claim 7 is narrower and requires the primer consisting of SEQ ID NO: 1. It is unclear whether the parentheses limits the claims or is merely an example. Clarification is required.
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.
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.
Claims 1 is/are rejected under 35 U.S.C. 103 as being unpatentable over OsicKa et al. (Infection and Immunity, Vol. 69, NO. 9, pages 5509-5519, September 2001) in view of Lee et al. (Frontiers in Microbiology, Vol. 6, Article 1548, January 2018) and further in view of Genbank L06302.1. (August 21, 2001).
OsicKa teaches Neisseria meningitidis RTX protein FrpC and FrpA differentiate serotypes (abstract). Osicka teaches primers and conditions for amplifying frpA loci (see Table 1, page 5510).
OsicKa does not teach LAMP primers or methods of detecting Neisseria meningitidis iron-regulated protein (frpA) gene with LAMP primers of SEQ ID NO: 1-8.
However, Lee teaches loop-mediated isothermal amplification assay for Serogroup identification of Neisseria meningitidis in cerebrospinal fluid. Lee teaches LAMP methods for identification of N. meningitidis using LAMP (abstract). Lee teaches LAMP primer design was performed using PrimerExplorer V4 software and targeted different genes. Lee teaches different LAMP primers with 20-24 bp and 48-49bp in length. Lee teaches LAMP methods are rapid, sensitive and uniquely serogroup specific that have application in clinical laboratories and public health surveillance systems (abstract).
Genbank L06302.1 teaches Neisseria meningitidis iron-regulated protein (frpA) gene.
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Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention to have modified the PCR methods of Osicka for detecting Frpa for differentiating serotypes with LAMP methods taught by Lee to be rapid, sensitive and specific. The ordinary artisan would be motivated to have with a reasonable expectation of success, since: (i) Oscika teaches designing primers for the known FrpA gene, (ii) frpA regions of Neisseria meningitidis was known in the art as Genbank L06302 and (iii) Lee teaches rules for designing amplification primers and disclosed a publicly available program that uses the rules to design primers for any know target nucleic acid, specifically Lee teaches using the PrimerExplorer V4 software to design LAMP primers for known regions. An alignment of the claimed primers of the instant application to the known full length frpA sequences is provided above. The combination of references would have suggested a finite number of possible LAMP primer pairs that could be designed in FrpA . Designing primers to known regions is prima facie obvious absent unexpected results.
With respect to Claim 3, the combination of references teaches a method of
using the primers for detecting Neisseria meningitidis bacteria using LAMP at 63-65degrees C for 60 minutes (page 3, col. 2).
Response to Arguments
The response traverses the rejection. The response asserts Claim 1 recites a specific combination of six primers for performing LAMP. This argue has been reviewed but is not persuasive. The claim is directed to a genus of primers since the claims are directed to a sequence at least 90% identical to SEQ ID Nos. SEQ ID NO: 3 is 22 nts in length and thus, encompasses at least 2 alterations at any positions as well as additions or subtraction of nucleotides at the 5’ or 3’ ends. The claim is not directed to specific primers as argued by the response.
The response argues there is no reasonable expectation of success of arriving at this particular combination disclosed in the specification as providing rapid results in a highly sensitive method. This argument has been considered but is not convincing because the specification does not provide any unexpected results for the claimed primers. First, the claims are not limited to any particular primers. The response argues the claims are directed to a particular combination of primers, however the claims are not limited to a particular combination of primers. Thus, the results argued by the response are not commensurate in scope.
Second, with respect to “unexpected results”, the results should be unexpected. The instant specification states that LAMP primer assays are rapid and have high sensitivity. Lee teaches LAMP assays are rapid and sensitive (see abstract). Neither the response nor the specification compares the claimed primers to any other primers to show the claimed primers are unexpected.
The response argues the results are rapid, in less than 15 minutes, however Claim 3 requires the amplification was performed for 40 minutes, thus, the claims are not directed to the alleged unexpected results. Lee teaches performing LAMP reactions at 63-65degrees. 64 degrees is within this range and thus meets the limitation of Claim 3. With respect to the time, Lee teaches 60 minutes, however it would have been routine optimization to modify and alter the conditions to achieve improved results.
Thus for the reasons above and those already of record, the rejection is maintained.
Claims 3, 5, 7 is/are rejected under 35 U.S.C. 103 as being unpatentable over OsicKa et al. (Infection and Immunity, Vol. 69, NO. 9, pages 5509-5519, September 2001) in view of Lee et al. (Frontiers in Microbiology, Vol. 6, Article 1548, January 2018) and further in view of Genbank L06302.1 as applied to Claim 1, above and further in view of NEB BioLabs WarmStart LAMP kit (DNA & RNA) (Instruction Manual, Version 6.0_3/23, published in 2020).
Osicka, Lee nor Genbank teaches a temperature profile of 68C and 40min.
However, OsicKa teaches the LAMP mixture was incubated at 63-64C for 60 minutes and then heated at 80C for 2 min to terminate the reaction.
Lee teaches concentration of primers FIP and BIP at 1.6uM; F3 and B3 at 0.2 uM and LF and LB at 0.4uM. These concentrations are the same ratio used in Claim 7.
Further, BIOLABs WarmStart LAMP kit protocol calls for incubating at 65C for 30 minutes and time can be extended as necessary for very low copy targets, challenging sample types or reactions known to produce slower amplification times. The protocol then teaches the reaction can be inactivated by heater at 80C for 5 minutes. BioLabs also teaches primer concentrations in the same ratio.
Therefore, it would have been obvious prior to the effective fling date of the claimed invention to have optimized LAMP reactions, including primer concentrations and temperature profiles. The references teach LAMP primers, concentrations and temperature profiles may be optimized for particular analysis and experiments. It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). One skilled in the art would have known to optimize temperature profiles and primer concentrations. Osicka and BIOLABS each discuss temperature and concentrations for LAMP. Thus, the recited temperature and concentration values of the claims would be arrived at by routine experimentation by one of ordinary skill in this art. Also, they are results effective variables as they determine the diagnostic assay result, positive or negative diagnosis for example.
Claims 9 is/are rejected under 35 U.S.C. 103 as being unpatentable over OsicKa et al. (Infection and Immunity, Vol. 69, NO. 9, pages 5509-5519, September 2001) in view of Lee et al. (Frontiers in Microbiology, Vol. 6, Article 1548, January 2018) and further in view of Genbank L06302.1 and further in view of NEB BioLabs WarmStart LAMP kit (DNA & RNA) (Instruction Manual, Version 6.0_3/23, published in 2020) as applied to Claims 3, 5, 7 above and further in view of Hayashida et al. (PLOS Neglected Tropical Diseases, DOI: 10.1371, March 13, 2015) and Nyan et al. (Clin Infect Dis. Vol. 59, No. 1, pages 16-23, April 2014).
Osicka, Lee, Genbank nor NEB teaches using Trehalose and mannitol as a component of LAMP kits or methods.
However, Hayashida teaches improvements in LAMP protocols and kits to extend the technique to on-stie diagnoses of infections disease on site in remote areas (abstract). Hayashida teaches incorporating trehalose as cryoprotectant to prolong shelf-life of LAMP reagents at ambient temperatures and during lyophilization (Page 7, para 2).
Nyan teaches a mannitol-acetate buffer is used in LAMP reactions to allow storage at room temperatures for approximately 6 months and then evaluated in LAMP.
Therefore, it would have been prima facie obvious prior to the effective filing date of the claimed invention to have incorporated Trehalose and mannitol for the expected benefits taught by Hayashida and Nyan. The ordinary artisan would have been motivated to have modified LAMP kits to comprise trehalose for lyophilization of the necessary LAMP reagents to greatly increase the shelf-life of LAMP reagents and utility of LAMP as a point of need diagnostic in remote areas where access to sophisticated laboratory equipment would otherwise be limiting for access to diagnosis. Further the art teaches addition of mannitol buffer allows for room temperature storage for extended periods.
Conclusion
No claims allowable over the art.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 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 nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANINE ANNE GOLDBERG whose telephone number is (571)272-0743. The examiner can normally be reached Monday-Friday 6am-3:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu-Cheng (Winston) Shen can be reached on (571) 272-3157. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANINE A GOLDBERG/Primary Examiner, Art Unit 1682
June 15, 2026
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