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 . Applicant’s amendment filed 1/29/2026 is acknowledged. Claims 1, 2, 6, 9, 13, 17, 20, 22, 24, 32, 39 have been amended. Claims 3, 5, 7-8, 10-12, 14-16, 19, 27-31, 36-38 and 40 have been canceled. Claims 1-2, 4, 6, 9, 13, 17-18, 20-26, 32-35 and 39 are pending. All of the amendment and arguments have been thoroughly reviewed and considered.
Any rejection not reiterated in this action has been withdrawn as being obviated by the amendment of the claims.
This action is made Final.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Previous Rejections
Status of the Previous rejections
-The objection to the specification is withdrawn in view of Applicant’s amendment to the specification.
-The claim rejection under 35 USC 112(b) as being indefinite is withdrawn in view of the new grounds(s) of rejections necessitated by Applicant’s amendment of the claims.
-The claim rejection under 35 USC 101 is withdrawn in view of the new grounds(s) of rejections necessitated by Applicant’s amendment of the claims.
-The prior art rejection under 35 USC 102(a)(1) as being anticipated by Lorenzetti et al is withdrawn in view of Applicant’s amendment of the claims.
-The prior art rejection under 35 USC 102(a)(1) as being anticipated by Moustafa et al is withdrawn in view of Applicant’s amendment of the clams.
-The prior art rejection under 35 USC 102(a)(1) as being anticipated by Shi et al is withdrawn in view of Applicant’s amendment of the claims.
-The prior art rejection under 35 USC 103 as being unpatentable over Shi or Moustafa in view of He and further in view of Zhang et al is withdrawn in view of Applicant’s amendment of the claims.
New Ground(s) of Rejections
THE NEW GROUND(S) OF REJECTIONS WERE NECESSITATED BY APPLICANT’S AMENDMENT OF THE CLAIMS:
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.
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 1-2, 4, 6, 9, 13, 17-18, 20-26, 32-35 and 39 are finally 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.
(a) Claims 1-2, 4, 6, 9, 12-12, 17-18, 20-23 are indefinite in the claim 1 because the claim appears to recite a “use” without setting forth any steps involved in the process (assay). It is unclear how a LAMP assay comprising at least one loop-mediated isothermal amplification (LAMP) primer set which targets a DNA fragment(s) of a pathogen(s) associated with a bovine respiratory disease (BRD) result in an assay and having a limit of detection (LoD) of at least 103 results in a single-step identification of the pathogen without extracting nucleic acids from the sample. No positive, active method steps are recited. Additionally, the limitation “configured to provide” in the ‘wherein clause’ does not limit the claims to any particular method steps or provide any specific structure of the at least one LAMP primer set or provide guidance on how one is to establish the LoD of at least 103 for the primer set. A clear interpretation cannot be ascertained. See also MPEP which states “While minute details are not required in method claims, at least the basic steps must be recited in a positive, active fashion” (see ex parte Erlich, 3 UsPQ2d1011, p.1011 (Bd. Pat, Applicant. Int.1986)).
(b) Claims 24-26 are indefinite in the claim 24 at the recitation of “Primer Set Nos: A-AAAA because the metes and bounds of the limitation is unclear. The recitation of the limitation A-AAAA of the for the primer set ID Nos: does not provide any meaningful value to the primer sets or sequence identifiers. MPEP 2173.05(s) states: “[W]here possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience. “Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted)”. To overcome the rejection, it is suggested inserting the numerical value for the desired sequence identifiers into the claims (see e.g., MPEP 2412.04).
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.
6. Claims 1-2, 4, 6, 9, 13, 17-18 and 20-23 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims(s) do not fall within one of the four categories of patent eligible subject matter because the claims recite a use without delineating the method steps of how the method is performed. MPEP 2173.05q states “[u]se claims that do not purport to claim a process, machine, manufacture, or composition of matter fails to comply with 35 USC 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961)(“one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101”)”. Additionally, the limitation “configured to provide” in the ‘wherein clause’ does not limit the claims to any particular method steps and therefore does not impart meaningful limits to the claimed assay. MPEP further states “it is appropriate to reject a claim that recites a use but fails to recite steps under 35 U.S.C. 101 and 35 U.S.C. 112(b) if the facts support both rejections. In this case no specific step are provided therein such that a clear interpretation can be ascertained.
Although a claim should be interpreted in light of the specification disclosure, it is generally considered improper to read limitations contained in the specification into the claims. See In re Prater, 415 F.2d 1393, 162 USPQ 541 (CCPA 1969) and In re Winkhaus, 527 F.2d 637, 188 USPQ 129 (CCPA 1975), which discuss the premise that one cannot rely on the specification to impart limitations to the claim that are not recited in the claim. In view of the foregoing, the rejection under 35 USC 101 applies.
Claim interpretation
7. The claims 1, 24 and 32 recites the negative proviso, “without extracting nucleic acids from the sample”. MPEP states "[A]ny negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) (“[the] specification, having described the whole, necessarily described the part remaining.”).
The claim 1 further recites the wherein clause, “wherein the assay is configured to provide single step identification of the pathogen”. MPEP 2111.04 states the Court noted that a “wherein” or “whereby” clause in a method claim is not given weight when it simply expresses the intended results of a process step positively recited. In this case the claim 1 do not recite any positive, active step. Accordingly, the wherein clause recited in the claim 1 is not given any patentable weight.
Thus, for the purpose of application of prior art, the claims are being given the broadest, reasonable interpretation.
Claim Rejections - 35 USC § 103
7. 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.
8. 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.
9. 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.
10. Claim(s) 1, 2, 4, 6, 9, 12, 13, 17, 18, 21, 22, 23 and 32 is/are rejected under 35 U.S.C. 103 as being unpatentable over Moustafa et al (AJVR, vol. 78, no. 2, pages 134-143, February 2017) (citation made of record in prior Office action) in view of Shi et al (CN 106755462, May 31, 2017, citations are based on English translated document made of record in prior Office action.
Regarding claim 1 and 32, Moustafa et al teach a loop-mediated isothermal amplification (LAMP) assay comprising at least one LAMP primer set that targets a deoxyribonucleic acid (DNA) fragment of a pathogen associated with a bovine respiratory disease (BRD) in a sample, wherein the assay allows for single-step identification of the pathogen (Abstract and “Material and Methods”). Moustafa et al teach wherein the assay can process and provide a visual result in 60 minutes or less (28 minutes) the visual result indicative of the presence or absence of the pathogen in the sample (Abstract and page 140, col. 1 second full paragraph). Moustafa et al teach wherein the pathogen is P. multocida and the targeted DNA fragment comprises a gene consisting of kmtl (pages 135 and 139).
With regards to the negative proviso recited in the claims, any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining."). See also Ex parte Grasselli, 231 USPQ 393 (Bd. App. 1983), aff’d mem., 738 F.2d 453 (Fed. Cir. 1984). In this case, the specification teaches performing an extraction [00178] and the absence of an extraction step ([0075]). Therefore, the limitation is not given any patentable weight in the claims as recited.
Regarding claim 2, Moustafa et al wherein the pathogen associated with BRD is a bacterium associated with respiratory pathogens (Abstract).
Regarding claim 4, Moustafa et al wherein the pathogen is selected from the group consisting of Pasteurella multocida (P. multocida) (Abstract and “Materials and Methods”, page 135).
Regarding claim 6, Moustafa et al teach wherein the assay can process and provide a visual result in 60 minutes or less (28 minutes) the visual result indicative of the presence or absence of the pathogen in the sample (Abstract and page 140, col. 1 second full paragraph).
Regarding claims 9 and 18, Moustafa et al teach the sample wherein the sample comprises a colorimetric that is magnesium sensitive (“Materials and Methods”, pages 135-138).
Regarding claim 13, Moustafa et al teach wherein the pathogen is P. multocida and the targeted DNA fragment comprises a gene consisting of kmtl (pages 135 and 139).
Regarding claim 17, Moustafa et al teach wherein each of the LAMP primer sets is coupled with a colorimetric reagent (page 136-138).
Regarding claim 21, Moustafa et al teach wherein each LAMP primer set is at least about 98% specific to the targeted DNA fragment (Abstract and page 138).
Regarding claim 22, Moustafa et al teach further comprising a fluorescent indicator (page 138 and Figure 4).
Regarding claim 23, Moustafa et al teach further comprising wherein each of the least one LAMP primer set comprises 4 to 6 primers (pages 135-136, HS-LAMP Primer Design).
Moustafa et al do not recite the limit of detection of at least 103 copies/reaction for each LAMP primer set used in the LAMP assay.
Regarding claims 1 and 32, Shi et al teach a loop-mediated isothermal amplification (LAMP) assay and kit comprising at least one LAMP primer set that targets a deoxyribonucleic acid (DNA) fragment of a pathogen associated with a bovine respiratory disease (BRD) in a sample, wherein the assay allows for single-step identification of the pathogen (Abstract and entire document, esp. pages 4-7 and claims). Shi et al teach wherein each of the LAMP primer sets has a limit of detection (LoD) of at least 103 copies/reaction (pages 6 and 11). Shi et al teach wherein the assay can process and provide a visual result in 60 minutes the visual result indicative of the presence or absence of the pathogen in the sample (pages 6-8 which teaches the complete assay in 60 minutes). Shi et al teach wherein the pathogen is P. multocida and the targeted DNA fragment comprises a gene consisting of kmtl (page 7 and claims).
Regarding claim 2, Shi et al wherein the pathogen associated with BRD is a bacterium associated with respiratory pathogens (pages 2 and 6, claims).
Regarding claim 4, Shi et al wherein the pathogen is selected from the group consisting of Pasteurella multocida (P. multocida) (pages 2 and 6, claims).
Regarding claim 6, Shi et al teach wherein the assay can process and provide a visual result in 60 minutes the visual result indicative of the presence or absence of the pathogen in the sample (pages 6-8 which teaches the complete assay in 60 minutes).
Regarding claim 9, Shi et al teach wherein the sample is a bovine liquid sample and further comprising using a compound that is a magnesium or pH indicator (page 6).
Shi et al teach wherein each of the LAMP primer sets has a limit of detection (LoD) of at least 103 copies/reaction (pages 6 and 11).
Regarding claim 13, Shi et al teach wherein the pathogen is P. multocida and the targeted DNA fragment comprises a gene consisting of kmtl (page 7 and claims).
Regarding claim 17, Shi et al teach wherein each of the LAMP primer sets is coupled with a colorimetric reagent (page 6-8).
Regarding claim 18, Shi et al teach wherein the colorimetric reagent is pH sensitive or magnesium sensitive (page 6).
Regarding claim 21, Shi et al teach wherein each LAMP primer set is at least about 98% specific to the targeted DNA fragment (page 6).
Regarding claim 22, Shi et al teach further comprising a fluorescent indicator (abstract and pages 4-7)
Regarding claim 23, Shi et al teach wherein each of the least one LAMP primer set comprises at least 4 primers (Abstract and pages 7, and claims).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date of the claimed invention to have combined the method of Moustafa with that of Shi because both the teachings of Moustafa and Shi are of similar scope and incorporating the method steps or reagents as taught by Shi with those of Moustafa would not negatively alter or modify results of detecting a bovine respiratory disease with a loop-mediated isothermal amplification assay as taught by both references. The combination of the cited prior art is prima facie obvious in the absence of secondary consideration.
12. Claim(s) 20, 24-26, 32-35 and 39 is/are rejected under 35 U.S.C. 103 as being unpatentable over Moustafa et al in view of Shi as previously applied above in view of He et al (CN 108315401, July 2018 and translated documents) and further in view Zhang et al (CN 111057749, April 2020).
Regarding claims 20 and 24-26, 32-35 and 39, Shin et al or Moustafa et al teach a method and kit for a loop-mediated isothermal amplification assay comprising: providing at least one LAMP primer set that targets a deoxyribonucleic acid (DNA) fragment of a targeted pathogen associated with a bovine respiratory disease (BRD) in a sample; obtaining a sample from a subject; combining the sample and the at least one LAMP primer set into a mixture; heating the combination to initiate amplification of the targeted DNA fragment; and detecting a visual result indicative of the presence or absence of the targeted pathogen for BRD in the sample (see entire reference).
Moustafa in view of Shi do not teach wherein the LAMP primer set comprises one or more primers of SEQ ID NOS: 1-6, 25-30, 55-62, 99-110 and 147-158.
He et al teaches a PCR based method and primers for detecting a pathogen of bovine respiratory diseases wherein said pathogen is Pasteurella multocida (Abstract and page 4 and 5). He also teaches a sequence substantially identical to the sequence of SEQ ID NO: 2 (see alignment below and SEQ ID NO: 7 and para [0049] of the original document).
SEQ ID NO: 2
Pasteurella multocida.
CN108315401-A.
CC PD 24-JUL-2018.
Disclosure; SEQ ID NO 7; 16pp; Chinese.
Query Match 100.0%; Score 18; Length 21;
Best Local Similarity 100.0%;
Matches 18; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 CACTCACAACGAGCCATA 18
||||||||||||||||||
Db 19 CACTCACAACGAGCCATA 2
PNG
media_image1.png
297
616
media_image1.png
Greyscale
Shi et al in view of He does not expressly wherein in the method and kit the visual result encompass measuring visual result in the heated combination.
Moustafa does provide some teachings of the analysis of visual display of LAMP products. Moustafa teaches that results of LAMP reactions, which were run in a water bath or heat block, were made visible via UV illumination by addition of the fluorescent dye (page 136, last paragraph to page 137, lines 1-4). Moustafa et al teach concentration of the DNA sample were measured by use of fluorimeter. Sensitivity and specificity of the results were calculated and the ROC curve were constructed on the basis of the results (pages 136 and 137). Moustafa further teach the use of qPCR-based equipment for performing the assay and the use of portable reaction tubes (Figure 4).
Zhang et al provides a general teachings of a visual detection method of isothermal amplification products, wherein isothermal amplification method may comprise of LAMP assay for detecting all kinds of pathogens (see pages 1-3). Zhang teachers herein the visual detection method comprise of a nucleic acid sample to be detected after amplification, adding mixed indicator chromogenic reaction, wherein the mixed indicator comprises a method ion indicator and acid-base indicator and wherein the acid-base indicator may comprise phenol red and neutral red (see entire document, see page 4). Zhang et al teach the reaction system indicator can be performed in a reaction container without the need for special instruments (pages 4 -7 and claims).
The references do not expressly teach the presence of a camera in the method and kit. However, it would have been prima facie obvious to one of ordinary skill in the art at the time of the effective filing date of the claimed invention to have additionally encompass a camera in the LAMP method and kit as taught by Moustafa and Shi in view of He et al and further in view of Zhang et al for the obvious benefit of capturing and recording visual results from the LAMP assays taught by the combination of the method steps. Such addition would be in the ordinary artisan’s capability and would further enhance the effects of the of Shin et al.
Response to Arguments
13. Applicant traverses the rejection on the following grounds: Applicant traverses the teachings of Moustafa on the grounds that the reference analyzing LAMP products by electrophoresis and viewing bands under UC, and adding a fluorescent dye and inspecting tubes under UV light to visualize fluorescence. The references do not teach indicator based assays that include or are coupled with an indicator as part of the assay itself to yield to a direct, field usable visual readout without external instrumentation or post amplification manipulation. Applicant states that Moustafa additionally does not teach the required processing steps and single step visual indicator as well as the limit of detection required by the claim.
Applicant traverses the teachings of Shi and states that Shi et al does not operate on unprocessed sample and/or without extracting nucleic acids from the sample but instead requires multistep-physical manipulation and preparation to generate template DNA prior to amplification. Applicant states that Shi et al fails to disclose any assay that is configured to all single step identification of the pathogen and Shi teaches limit of detection in terms of CFU/ml and does not provide any conversion, disclosure or teaching that correlates CFU/ml to DNA copies per mi, particularly after centrifugation, washing and resuspension steps.
Applicant states that the teachings of Zhang and He does not cure the deficiencies of the Moustafa and Shi and accordingly the rejection should be withdrawn.
All of the amendments and arguments have been thoroughly reviewed and considered but are not found persuasive for the reasons that follows: The examiner acknowledges Applicant’s arguments but notes that the arguments are not commensurate in scope with the claims because the claims (e.g., claim 1) do not recited specific method steps but rather conclusory statements and intended use limitations that do not carry any patentable weight. The limitation “configured to” do not impart specific structural features or define any specific method steps with provides for single step identification. The wherein clause in the claim is recited at such a high level of generality that it does not carry any patentable weight (see MPEP 2111.04). With regards to the negative proviso regarding the lack of an extraction step, the specification teaches in one embodiment methodology occurring after extraction and in another embodiment the lack of an extraction step (see citation above). MPEP 2173,05(i) states any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. See In re Johnson, 558 F.2d 1008, 1019, 194 USPQ 187, 196 (CCPA 1977) ("[the] specification, having described the whole, necessarily described the part remaining."). See also Ex parte Grasselli, 231 USPQ 393 (Bd. App. 1983), aff’d mem., 738 F.2d 453 (Fed. Cir. 1984). Thus this argument is deemed moot.
In review of Applicant’s arguments concerning the limit of detection (LoD), the claims as currently written do not provide any specific calculations or methodologies regarding how the LoD is determined or what is required to make the determination effective for the primers to be used in the claimed invention. Applicant is reminded that although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Applicant’s arguments are not found persuasive to obviate the teachings of the cited prior art.
Conclusion
14. No claims are allowed. 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.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CYNTHIA B WILDER whose telephone number is (571)272-0791. The examiner can normally be reached Flexible.
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/CYNTHIA B WILDER/Primary Examiner, Art Unit 1681