Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-12, and the species of the Salmonella genus and the Listeria genus in the reply filed on November 26th, 2025 is acknowledged.
Claims 13-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 16th, 2025.
Applicant comments about the species in their remarks filed November 26, 2025. As a clarification, the single elected species referred to the list of pathogens recited in claims 11 and 12. It is understood that some of those pathogens are a genus of pathogens. Thus, while the single elected species is the Salmonella genus and the Listeria genus, these encompass all of the phylogenic species of Salmonella and Listeria.
Upon searching the examiner identified prior art which includes the species of Enterobacteriaceae family, Salmonella genus, Listeria genus, Staphylococcus genus, and Shiga toxin-producing E. coli of Zegrati. The species election in claim 11 and 12 has been expanded to include these species.
Status of Claims
Claims 1-16 are currently pending. Claims 13-16 are withdrawn from consideration as being drawn to a non-elected invention/species. Claims 1-12 are under examination and discussed in this Office Action.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on July 24th, 2023 and January 3rd, 2024 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 9 and 12 are objected to because of the following informalities:
Claim 9 is objected to because of the following informalities: the term “preforming” appears to be a typographical error. Appropriate correction is required.
Claim 12 is objected to because of the following informalities: duplicate conjunction [“and”] in the last two lines of the claim.
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.
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.
Claim 9 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 9 recites the limitation "wherein the lysis step (2)" in line 1. There is insufficient antecedent basis for this limitation in the claim. There is no “step (2)” in claim 1 from which the claim depends.
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.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Claims 1-12 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In making a determination of whether the application complies with the written description requirement under 35 U.S.C. 112[a] or 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is claiming and what Applicant has possession of. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that 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. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was “ready for patenting” such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991). See MPEP § 2163.
Claim 1 recites “…a pre-enrichment step comprising adding the sample to a pre-enrichment medium so as to obtain a pre-enriched sample,” The claim as written appears to embrace a method wherein any pre-enrichment medium capable of producing a “pre-enriched sample” without limitation as to the composition, preparation, or defining characteristics of the pre-enrichment medium.
Regarding claim 1, the specification does not clearly describe or define what constitutes a “pre-enrichment medium” within the scope of the claim, for instance, paragraph [0011] merely states that the sample passes through a pre-enrichment step in a pre-enrichment medium, without describing the medium itself. Paragraph [0021] indicates that the pre-enrichment medium “can, for example, be a non-selective pre-enrichment” and “can, for example, not have antibiotics” while paragraph [0022] alternatively states that the medium “can, for example, be a selective pre-enrichment medium”. These cited descriptions provide a non-exhaustive list of examples from the specification and does not define the composition, functional requirements, or distinguishing characteristics of the pre-enrichment medium. Finally, paragraph [0030] – [0031] describes an embodiment in which a food sample is incubated in a volume of non-selective pre-enrichment medium at a specific temperature and time duration. This description is also limited to a particular example and it indicates some amount of ambiguity as it does not establish what properties or components are required for a medium to be a “pre-enrichment medium”. The specification does not describe how the medium is formulated, what components are necessary, or how the medium ensures pre-enrichment of a plurality of different pathogens across the full scope of the claim. Therefore, it cannot be said that there is a definitive description of pre-enrichment medium. Moreover, because the specification or claim does not provide adequate description of pre-enrichment medium, it likewise does not describe the “pre-enrichment sample”. Without knowing what the pre-enrichment medium entail, it is unclear what is present in the pre-enriched sample prior to the lysis step. It is also noted that claims 9 and 10 suffer from the same issue of not providing adequate description of pre-enrichment medium and pre-enriched sample. Based on the specification, the Applicant does not have possession of the method as claimed.
Claims 2-12 depend from claim 1, inherit these deficiencies, and are rejected on the same basis.
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.
Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Zegrati et al (WO 2016/164407) in view of Pourquier et al (WO 2022/101583).
Zegrati et al teaches a method for detecting one or more pathogens in a sample comprising: a pre-enrichment step in which a sample comprising one or more pathogens is enriched in a rich and non-selective medium [Claim 1]; a lysing step in which pathogens in the enriched sample are lysed using thermal, chemical, enzymatic, and/or mechanical lysing methods [0153-0154]; a detection step in which amplification and detection of pathogen nucleic acids, including multiplex PCR detection of multiple pathogens [Claims 3-4; 0243-0244]. In view of the 112b rejection above, the specific components of the pre-enrichment step have not been defined. Therefore, the enrichment step of Zegrati et al reads on the instant claim.
Zegrati et al also teaches that lysis and detection workflow may involve sequential processing step, including further handling of lysates prior to amplification depending on assay designs [0154, 0157, 0159]. Zegrati et al further teaches performing multiple lysis steps to amplification, including sequential lysis steps conducted at different temperatures [claim 3-4].
However, Zegrati et al does not teach terminating the lysis step before detection without increasing temperature. This deficiency is made up for in the teaching of Pourquier et al. Pourquier et al teaches terminating lysis by inactivation of a protease using a protease inhibitor without a heating step, followed by PCR detection [Claims 1-2].
Pourquier et al teaches an in vitro method comprising enzymatic lysis and protein denaturation, followed by inactivation of the protease without a heating step, and subsequent amplification performed directly on the resulting lysate [claim 1]. Pourquier et al further teaches the use of aminoethylbenzenesulfonyl fluoride hydrochloride [AEBSF] as a protease inhibitor for protease inactivation [claim 4].
Pourquier et al therefore explicitly teaches termination of lysis prior to PCR amplification without increasing temperature, in order to maintain downstream amplification.
It would have been obvious to one of ordinary skill in the art, before the effective filling date of the claimed invention to modify the method of Zegrati et al by terminating lysis prior to PCR amplification using the non-heating protease inactivation method taught by Pourquier et al, because Pourquier et al teaches that protease activity must be terminated prior to PCR amplification to permit enzymatic amplification to proceed.
Pourquier et al thus teaches that, following an initial lysis step, subsequent enzymatic processing steps are desirable performed at a lower temperature or without increasing temperature, in order to preserve nucleic acid integrity and compatibility with downstream amplification.
Regarding claim 2, Pourquier et al teaches performing PCR amplification directly on a lysate following termination of protease activity [Claims 1-2]. Zegrati et al teaches that lysates and reaction components may be processed further prior to amplification depending on assay requirements, and that reaction components may be added sequentially in any order [0154]. Zegrati et al further teaches dilution as part of sample and lysis preparation, including formation of a sample/lysis buffer mixture by diluting the lysis buffer with an aqueous medium at various volumetric ratios that encompass the claimed dilution range of 1:3 to 1:100 [0157].
Regarding claim 3, Pourquier et al teaches terminating lysis by adding a protease inhibitor to a lysate following protease-mediated lysis [Claim 1].
Regarding claim 4, Pourquier et al teaches the use of aminoethylbenzenesulfonyl fluoride hydrochloride (AEBSF) as a protease inhibitor for inactivating a protease following lysis [Claim 4].
Regarding claim 5, Pourquier et al teaches a lysing step performed out using a protease and termination of the lysis step by adding a protease inhibitor, followed by PCR amplification performed directly on the lysate without heating step [Claims 1-2]. Zegrati et al further teaches that lysates and reaction components may be processed further prior to amplification, reaction components may be added sequentially in any order, and lysis mixtures may be diluted with an aqueous medium prior to downstream nucleic acid analysis [0154], [0157].
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to first add a protease inhibitor to terminate the lysis reaction and subsequently dilute the lysate prior to performing multiplex PCR in order to facilitate downstream amplification and optimize assay performance.
Regarding claim 6, Pourquier et al teaches the use of aminoethylbenzenesulfonyl fluoride hydrochloride (AEBSF) as a protease inhibitor for inactivating a protease following lysis without heating [Claims 4]. Zegrati et al teaches dilution of a sample/lysis buffer mixture using an aqueous medium at various volumetric rations, including ratios that claimed dilution range of 1:10 to 1:75 [1587].
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to utilize AEBSF as the protease inhibitor and to dilute the lysate within the recited range prior to multiplex PCR.
Regarding claim 7, Zegrati et al teaches that components of a lysis reaction, including reagents such as protease inhibitors may be added sequentially in any order and further teaches dilution of a lysate as part of sample preparation prior to amplification and after a suitable period of agitation, the lysed sample is further processed [0154, 0157 and 0159], thereby explicitly teaching a temporal interval between lysis-related steps.
Regarding claim 8, Pourquier et al teaches performing PCR amplification directly on a lysate following protease-mediated lysis and inactivation of the protease using a protease inhibitor, without any intervening purification or nucleic acid isolation step [claim 1]. Therefore, the lysate used for amplification is a crude lysate.
Zegrati et al further teaches that nucleic acid purification may be performed as needed [0154], indicating that that purification is optional and not required in all embodiments, and downstream assays may be performed directly following cell lysis depending on assay requirements [154].
Regarding claim 9 Zegrati et al teaches performing multiple lysis steps prior to amplification, including sequential lysis steps conducted at different temperatures, including a first lysis followed by a second lysis at a different temperature [claims 3-4]. While Zegrati et al discloses the second lysis step as being performed at a temperature higher than the first lysis step, Zegrati et al teaches the general use of sequential lysis steps and multiple lysis modalities prior to amplification.
Pourquier et al teaches an in vitro method comprising enzymatic lysis and protein denaturation, followed by inactivation of the protease without a heating step, and subsequent amplification performed directly on the resulting lysate [claim 1]. Pourquier et al thus teaches that subsequent enzymatic processing following an initial lysis step may be performed at a lower temperature or without increasing temperature in order to maintain compatibility with downstream nucleic acid amplification.
It would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention to modify the sequential lysis methods of Zegrati et al by performing subsequent chemical, enzymatic, or mechanical lysis steps at a lower than an initial thermal lysis step, as taught by Pourquier et al. Therefore, the combination of Zegrati et al and Pourquier et al teaches a lysis step comprising first performing a lysis at a first temperature, followed by subsequently performing at least one of a chemical lysis, an enzymatic lysis, or a mechanical lysis at a second temperature that is lower than the first temperature, as recited in claim 9. For these reasons claims 1-6, and 8-9 are obvious over Zegrati et al in view of Pourquier et al.
Regarding claim 10, Zegrati et al teaches enriching a sample by suspending the sample in an enrichment medium prior to downstream detection. Zegrati et al discloses that the enrichment medium may be nonselective, as distinguished from selective media that contain selective agents such as antibiotics to inhibit competing microorganisms. Zegrati et al further discloses embodiments in which the sample is suspended in a rich and nonselective medium, including Buffered Listeria Enrichment Broth Base without supplements [0128], which lacks selective agents and therefore constitutes a non-selective pre-enrichment medium.
Regarding claim 11 and claim 12, Zegrati et al teaches detection of multiple pathogens including members of the Enterobacteriaceae family, Salmonella genus, Listeria genus, Staphylococcus genus, and Shiga toxin-producing E. coli [0019-121; 0243].
Conclusion
All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nura Choudhury whose telephone number is 571-272-6148. The examiner can normally be reached M-F, 9-5 ET.
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/NURA M. CHOUDHURY/Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683