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 election without traverse of Group I (claims 1-13 and 16-18) and election of species SEQ ID NOs: 14 and 29 in the reply filed on 07/09/2024 is reacknowledged. It is noted that Applicant’s 04/02/2026 claim amendments require nonelected species. In the interest of advancing compact prosecution, the Examiner withdraws the species election requirement, but maintains the Restriction requirement as between the Groups/Inventions.
Claims 23-25 are new.
Claims 2-4, 7, 14-15, 17, and 19-20 are cancelled.
Claims 1, 5-6, 8-13, 16, 18, and 21-25 are pending and under examination on the merits.
Withdrawn Objections and Rejections
The rejections of the claims under 35 USC §103 as presented in the previous office action are withdrawn and replaced with the rejections of the claims under 35 USC §103 as presented in this Office Action to better account for the new and different claim scope resulting from the 04/02/2026 claim amendments.
Maintained-Claim Interpretation
Note that the recited analyte-capture entity is being given its plain meaning in the art in light of the ambiguous definition of the instant specification (see pages 23-24 [“For clarity purposes and in the rest of the description, the molecule of interest is named an analyte-capture entity. It is to be noted that at least the 2 binding partners of the polypeptides on the support can comprise the same analyte-capture entity but advantageously different analyte-capture entities… In the frame of the invention, the analyte and/or the analyte-capture entity can be any type of molecules in terms of nature and function”] further noting that no embodiment would appear to have the cognate binding partner comprising the analyte-capture agent prior to contacting the cognate binding partner with the functionalized/immobilized polypeptide. Therefore art teaching the cognate binding partner comprising the analyte-capture entity at any point in the assay is deemed to read upon this limitation in light of the instant disclosure and present claim drafting).
Maintained-Claim Objections
Claim 6 is objected to for its dependence from rejected base claim 1. Claim 6 is deemed to contain allowable subject matter (a sequence comprising or consisting of the specified sequence portions) and would be deemed allowable if re-written in independent form.
Claim 9 remains objected to for its dependence from rejected base claim 1. Claim 9 is deemed to contain allowable subject matter (the full length SEQ ID NOs: 1-27) and would be deemed allowable if re-written in independent form.
Claim 23 is objected to for improper reference to Table 2 of the specification. The MPEP provides that “[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 parteFressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted),” (see MPEP §2173.05(s)).
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.
Claim 6 and 8-9 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.
Claims 6 and 8-9 recite the broad recitation “comprises”, and the claims also recite “consists of” which is the narrower statement of the range/limitation. Claims 6 and 8-9 are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. This is confusing and indefinite because the term "comprises" indicates that other non-recited elements can be included in the scope of the claims; yet, “consists of” is by its very nature, closed. This implies that there cannot be any additional embodiments outside those explicitly recited in the claims.
New-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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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, 5, 8, 10-13, 16, 18, 21-22, and 24-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over UAB (WO 2017100584 A1) in view of Kwon et al (Sensitive multiplex detection of whole bacteria using self-assembled cell binding domain complexes. Anal Chim Acta. 2018 Nov 7;1030:156-165; Electronically published 05/08/2018); as evidenced by do Carmo de Freire Bastos (Pharmaceuticals (Basel). 2010 Apr 19;3(4):1139-1161. doi: 10.3390/ph3041139)), University of Glasgow (WO 2016046218 A1), Walker et al (Nucleic Acid Research, 2002, 30(14), 3225-34; as cited on page 16 of the instant specification), and Uniprot (accession No. A0A0L8IMK8_PSESX; obtained from: https://www.uniprot.org/uniprotkb/A0A0L8IMK8/entry; available at least as of 11/11/2015 as evidenced by screen capture of Sequence alignment result from STIC).
Regarding claims 1, 5, and 8, UAB teaches compositions and methods for protein purification using polypeptides comprising a wild-type colicin-DNAse domain (noting that colicins are bacteriocins within the terms of the instant disclosure; see for example, table 1 of the instant specification at page 34) modified to comprise one or more mutations selected from the group consisting of a mutation that reduces DNAse activity, a mutation that decreases DNA binding, and a mutation that increases thermostability of the polypeptide. The polypeptides optionally comprise a heterologous polypeptide that is operably linked to a cleavable polypeptide sequence, wherein the cleavable polypeptide sequence links the heterologous polypeptide with the colicin-DNAse domain. UAB further teaches polypeptides comprising a colicin immunity protein, wherein the immunity protein comprises one or mutations that increase thermostability of the polypeptide (see for example, pages 1, 14, 25-26, 33, and 43-44 and claims 1-35 and 40 at pages 47-49). The polypeptides comprising a modified colicin immunity protein and/or the polypeptides comprising a bacteriocin DNAse domain can be immobilized on a solid support (see for example, the bottom of page 14 and claim 40).
UAB does not teach that the polypeptide comprising the colicin-domain (may be a full colicin) or the colin-immunity protein has a Kd of equal to or less than 10-10M for its cognate binding partner in an immunoassay.
However, Kwon et al teach functionalization of biotin-CBDs (cell wall binding domains, such as CBDSA, a domain taken from lysostaphin, which is known in the art to be a bacteriocin (as evidenced by do Carmo de Freire Bastos (Pharmaceuticals (Basel). 2010 Apr 19;3(4):1139-1161. doi: 10.3390/ph3041139)) which were immobilized on a support (a neutravidin-coated 96-well plate) (see for example, sections 1 and 2.5 at pages 157-158). Kwon et al teach that the binding affinity of CBDs is similar to that of an antibody for its antigen. Moreover, Kwon et al teach that like antibodies, cell wall binding domains (CBDs) from bacteriophage endolysins, bacterial autolysins, and bacterial exolysins (e.g., bacteriocins) are capable of binding to target bacterial cell walls (cognate binding partners) with high specificity. For example, the Listeria phage endolysin has a strong binding affinity (KD = 10-9 -10-8 M) for its cognate binding partner, as determined via surface plasmon resonance (SPR) analysis. In addition to the binding characteristics of CBDs, genetic information of numerous lysins for targeting bacterial pathogens is currently available thanks to advances in DNA sequencing technology. Because most lysins are comprised of modular structures, which include one catalytic domain and one or more CBDs, the genes encoding corresponding CBDs can be readily obtained from genetic sequencing databases (i.e., GenBank or EBI) (see for example, pages 157-158; noting this exemplary teaching supports that the art provides written description for the recitation of bacteriocins and their cognate immunity proteins).
Kwon et al does not specify that the bacteriocin CBD (CBDSA ) placed on the support has the claimed Kd for its cognate immunity partner.
UAB and Kwon do not clearly teach motivation to place at least two polypeptides, such as a bacteriocin and or/its cognate immunity protein on a support.
However, University of Glasgow teaches pyocins/klebicins/colicins which is/are disclosed to be useful in treating antibiotic-resistance, respiratory, bacterial infections through binding of the target portion of the pyocin/klebicin/colicin to some part of the surface of the target organism (e.g.: bacteria which the pyocin is able to target/bind) (see for example, pages 1-2, 9 and 40). Additionally, University of Glasgow teaches that, for gram-negative pathogens such as Pseudomonas aeruginosa (pyocin-based), Klebsiella pneumoniae (klebicin-based) ,and Escherichia coli (colicin-based) therapeutic options are often limited and an alternative strategy for the discovery of effective antibiotics is to exploit the potent narrow-spectrum antibiotics produced by many bacteria for intraspecies competition. In P. aeruginosa, K. pneumoniae and E. coli these take the form of multi-domain protein antibiotics known as the S-type pyocins, klebicins and colicins respectively (see for example, pages 1-2).
UAB, Kwon et al, and University of Glasgow, do not teach the sequence of instant SEQ ID NOs: 28. 29, or 30.
However, Walker et al teach that the H-N-H (ßßα-Me motif) of the cytotoxic domain of bacteriocins (such as colicin E9) has a sequence reading on instant SEQ ID NO: 28 (see for example, Figure 7 at the first sequence labeled Colicin E9 at page 3232). Walker et al further teach that the wildtype Colicin sequence (may be substituted with alanine (H to A substitution at positions 102 or 103) to prevent DNAse activity whereupon residue N118 is indicated as structurally important and whereupon a sequence encompassing instant SEQ ID NO: 29 is constructively taught in Figure 7 (see the Colicin E9 sequence having H102, A103) where motivation to substitute H103 for A is taught throughout where there is a desire to diminish/remove DNAse activity (see for example, pages 3225-3226 and 3228-3232 and figure 7).
UAB, Kwon et al, University of Glasgow, and Walker et al do not teach a bacteriocin or cognate immunity protein having a Kd equal to less than 1010M. However, Uniprot teaches the structure/sequence of a immunity protein of colicin E9, where said sequence is 100% identical to residues 333 to 420 of instant SEQ ID NO: 15 (see the provided alignment attached to this Office Action). Because claim 8 recites alternative structures, any one of which could be the protein having the recited Kd as required by claim 1, the immunity protein of Uniprot is presumed to have the recited Kd.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of UAB, Kwon et al, University of Glasgow, and Walker et al. The artisan would have been motivated to make and use the invention as claimed because Kwon et al provide motivation to use bacteriocins (bacteriocin CBDs) for determining the presence/absence of bacteria in a sample and show functionalization on a plate (support). Kwon et al supports that bacteriocins or their immunity proteins, reducing to practice immobilization of 3 CBDs, may be readily functionalized on the support by teaching said functionalization at a high level of generality and teaching that the CBDs (bacteriocins) may be selected from art-recognized databases of said polypeptides for use (see for example pages 157-158 and 160). UAB further teach that multiple different colicins and/or their immunity proteins may be immobilized on a support (see for example, claims 1-35 and 40 at pages 47-49). These teachings, when combined with the high level at which Kwon et al discuss attachment of the CBD to the support would have indicated to the artisan the predictability of such functionalization of any known bacteriocin/cognate immunity protein, where selection of the agent used would be up to the artisan for their desired use. Further, the art provides motivation because Kwon et al teach that multiplex detection (using more than 1 biomarker (more than 1 bacteriocin)) is particularly important to ensure accurate and simultaneous measurement of multiple bacterial species in a given sample, as discussed above (see for example, page 157).
The artisan would have been further motivated to assay for (place the pyocin/klebicin/colicin/bacteriocin and/or its cognate immunity protein on a support) through methods known in the art (such as the method of UAB and/or Kwon et al) in order to study or make use of said polypeptides for known uses such as treatment of respiratory infections as taught by University of Glasgow (see for example, page 40). Kwon et al do not specify that the bacteriocin used has the claimed Kd for its cognate immunity protein. The artisan would have been motivated to adapt the assay to comprise the pyocins/klebicins/colicins of University of Glasgow for two reasons. First, as mentioned above, the pyocins/klebicins/colicins of University of Glasgow is disclosed to be useful in treating antibiotic-resistance, respiratory, bacterial infections through binding of the target portion of the pyocin/klebicin/colicin to some part of the surface of the target organism (e.g.: bacteria which the pyocin is able to target/bind) (see for example, pages 1-2 and 9). Second, because providing a colicin/klebicin/pyocin and its cognate immunity protein provides a robust assay for which to test a sample for binding to screen for the presence of a colicin/klebicin/pyocin infection which is clinically important because as University of Glasgow teaches, for gram-negative pathogens such as Pseudomonas aeruginosa (pyocin-based), Klebsiella pneumoniae (klebicin-based) ,and Escherichia coli (colicin-based) therapeutic options are often limited and an alternative strategy for the discovery of effective antibiotics is to exploit the potent narrow-spectrum antibiotics produced by many bacteria for intraspecies competition. In P. aeruginosa, K. pneumoniae and E. coli these take the form of multi-domain protein antibiotics known as the S-type pyocins, klebicins and colicins respectively (see for example, pages 1-2). Further, where the immunity protein of colicin E9 of Uniprot comprises the required structure of claim 8, which is exemplary of the protein of claim 1, it is presumed to possess the claimed properties (such as the claimed Kd for its cognate binding partner). The MPEP further provides that, “[p]roducts 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. Id,” (see MPEP section 2112.01 (II)). The artisan would have been motivated to make and use the invention as claimed because Walker teaches a sequence encompassing instant SEQ ID NO:29 as a functional equivalent where the substitution of H to A at position 103 reduces DNase activity (see for example, pages 3225-3226 and 3228-3232 and figure 7). The artisan may have been motivated to diminish DNAse activity in order to use the colicin in the assay without damaging the bacteria to be detected. The artisan would have found it obvious to include the variants encompassed by instant SEQ ID NOs: 28, 29, and 30 as a quality control to ensure that all 3 were able to efficiently function in an assay using the support and to determine whether the H102A (encompassed by instant SE ID NO: 28) and/or H103A (encompassed by instant SE ID NO: 29) mutants were more stable for binding target during the assay without target degradation/damage relative to one another and relative to the wildtype sequence encompassed by instant SEQ ID NO: 28. The artisan would have had a reasonable expectation of success based on the cumulative disclosure of these prior art references.
Regarding claims 10-13 and 18, as briefly discussed above, Kwon et al teach that CBD-SA-GOx complexes (believed to read upon the recitation of the analyte-capture entity (which is a polypeptide as recited by instant claim 18) where the GOx portion reads on the limitation of a labeled detection entity as recited by instant claim 13) and immobilized CBDs (including the CBD from lysostaphin, which is a bacteriocin) were then used to detect target bacteria via a CBD-based sandwich immunoassay. This concept involves the initial binding of biotin-CBD to neutravidin on the surface of 96-well plates (see for example, section 2.5 at page 158). Kwon et al teach that the plate/support is contacted with a reaction mixture comprising bacteria (cognate binding partners) which bind to the CBD-coated plate through washing/incubation with a liquid reagent (held to read on the reaction mixture of instant claim 10), bacterium-specific CBD-SA-GOx complexes (analyte capture entities with a detection label)) are then contacted with the support whereupon the CBD-SA-GOx complexes bind selectively to their target bacteria (cognate binding partners). The CBD-SA-GOx complexes, bound to their respective target bacteria, then generate H2O2 in the presence of glucose as a result of GOx-catalyzed glucose oxidation. Kwon et al then used a commercial H2O2 detection kit, based on the color change of xylenol orange due to ferrous ion oxidation, which allowed them to determine the detection level of H2O2 produced from GOx (see for example, sections 2.5 and 3.2 and Figure 2A at pages 157-160).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references. The artisan would have been motivated to make and use the invention as claimed because Kwon et al teach that multiplexed detection is important for bacterial identification and further teach that their assay is an effective means of accomplishing said multiplexed detection with accuracy (see for example pages 157-158 and 160). Where claim 11 recites that the reaction mixture comprises cognate binding partners which comprise an analyte-capture entity, UAB, Uniprot, Walker et al, Kwon et al, and University of Glasgow do not teach pre-incubation of the analyte capture entity (the CBD-SA-GOx complexes), but Kwon et al teach that the analyte capture entity binds the cognate binding partners (bacteria)(see for example pages 157-158 and 160). This is presumed to read on the limitation of claim 11. In the alternative, preincubation of the complexes and the bacteria (or direct labeling of the bacteria with the SA-GOx) would have been an obvious matter of choice for the artisan. As part of determining obviousness, it is to be considered that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation, § 103 may bar its patentability. When considering obviousness of a combination of known elements, the operative question is thus “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (see MPEP 2141. I.)). This would have been presumed to yield no more than the predictable result of enabling detection of the immobilized bacteriocin/immunity protein through detecting H2O2 produced by the cognate-binding partner-SA-GOx complex bound to the immobilized polypeptide. The high level of generality employed by the prior art implies that the components (the bacteriocin, immunity peptide, and SA-detection label) are modular and may be logically re-organized or preincubated. It is further noted that the reaction mixture of claim 10 is not required for use at any particular point in the assay of UAB as modified by Kwon, Uniprot, Walker et al, and University of Glasgow, such that the point where known teaches that the immobilized protein binds the CBS-SA-GOx complex, is deemed to read upon and make obvious the limitations of claims 10-11.The artisan would have had a reasonable expectation of success based on the cumulative disclosure of these prior art references.
Further regarding claims 12-13, while Kwon et al do not specifically use the language “kit” as recited at the claim preamble, in the instant case, it is noted the terminology “kit” is not found to further limit the scope of the claims beyond requiring the inclusion of the reagents/reaction mixture (taught by UAB, Uniprot, Walker et al, Kwon et al, and University of Glasgow, as discussed above), as it does not clearly invoke any additional ingredients or provide the antecedent basis for terms appearing in the body of the claim (such as specific packaging or container elements, for example). See MPEP 2111.02. Consequently, when the claims are given their broadest reasonable interpretation, because the combination of cited prior art references teaches the same structural components that applicant refers to as a kit, the teachings of the prior art address the claimed elements/limitation even though the references does not employ the word “kit” in describing their invention, as the references teaches all necessary reagents of the claimed “kit”.
If the prior art structure(s) is capable of performing the intended use, then it meets the claim. Applicant is also reminded that claim scope is not limited by claim language that does not limit a claim to a particular structure. See MPEP 2111.04. In this case, no clear structural differences are invoked by the recitation of instant claims 12-13. Because there is no distinction between the claimed structure(s) and that of the cited prior art, it is the case that reagents/reaction mixture would similarly be expected to be capable of functioning in the kit as needed to make obvious the product claimed. Therefore, the combined references are held to make obvious as of the filing date the limitations of instant claims 12-13, giving the artisan a reasonable expectation of success based on the cumulative disclosure.
Regarding claim 16, it would appear that one of the peptides encompassed within the recitation of the at least two peptides as taught by Kwon et al is a bacteriocin (functionalized on the support) then washed with cognate binding partners (bacteria). Kwon et al teach that 3 CBDs are functionalized on a support and used in an immunoassay with success (see for example, pages 157-158 and 160). UAB teaches multiple colicin polypeptides and immunity proteins which may be functionalized on a support (see for example claims 1-35 and 40). There is nothing in Kwon et al or UAB to teach or suggest that the disclosed bacteriocins and/or their cognate immunity proteins cannot be combined on a support for use in an immunoassay. Therefore, the combination of 2 bacteriocins or 2 bacteriocin immunity proteins is deemed to be made obvious in light of the teachings of Kwon et al and UAB. The artisan, having a reasonable expectation of success in view of the cumulative disclosure, would have been further motivated to combine 2 such polypeptides because Kwon et al teach that multiplex detection (using more than 1 polypeptide/bacteriocin) is particularly important to ensure accurate and simultaneous measurement of multiple bacterial species in a given sample, as discussed above (see for example, page 157).
Regarding claims 21-22, as mentioned above, Kwon et al teach that bacteriocins have a high affinity for their cognate binding partners with KD = 10-9-10-8 M (see for example, pages 157-158 and 160 and section 2.5). Further, University of Glasgow, teaching a pyocin with the required structure of claim 6 (which is an exemplary polypeptide of claim 1), is presumed to teach a bacteriocin having the claimed Kd because, as discussed above, where the required structure is taught in the art, the art product is presumed to possess the claimed properties which are inseparable from the product because function flows from structure.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of UAB, Kwon et al, and University of Glasgow. The artisan would have been motivated to make and use the invention as claimed because Kwon et al teach a system for multiplex detection using high affinity bacteriocins and further teach that multiplex detection is particularly important to ensure accurate and simultaneous measurement of multiple bacterial species in a given sample (see for example, pages 157-158 and 160). The artisan would have had a reasonable expectation of success based on the cumulative disclosure of these prior art references.
Regarding claims 24-25, as discussed above, University of Glasgow teaches that, for gram-negative pathogens such as Pseudomonas aeruginosa (pyocin-based), Klebsiella pneumoniae (klebicin-based) ,and Escherichia coli (colicin-based) therapeutic options are often limited and an alternative strategy for the discovery of effective antibiotics is to exploit the potent narrow-spectrum antibiotics produced by many bacteria for intraspecies competition. In P. aeruginosa, K. pneumoniae and E. coli these take the form of multi-domain protein antibiotics known as the S-type pyocins, klebicins and colicins respectively (see for example, pages 1-2).
It would have been prima facie obvious for the artisan to use any one or more of the bacteriocins of University of Glasgow for the support of UAB as modified by the additional cited prior art references in order to assay for bacteriocins/immunity proteins associated with gram-negative infection to guide treatment, as discussed above. The artisan, given the generic disclosure of colicins would have found it obvious and predictable to look to the prior art for E9 E.coli colicins to use and would have found it obvious to use the E9 colin of Walker et al, with a reasonable expectation of success.
Claim(s) 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over UAB in view of Kwon et al as evidenced by do Carmo de Freire Bastos, University of Glasgow, Walker et, and Uniprot, as applied to claims 1, 5, 8, 10-13, 16, 18, 21-22, and 24-25 above, in further view of NCBI (accession No: VCW48573; available at least as of 11/09/2018; a colicin E9) and/or NCBI (Accession No: AAA23069; available at least as of 07/23/2016; a colicin E9 immunity protein).
Regarding claim 23, it is reasonably clear that the sequences referred to by NCBI accessions numbers must have been known in the art prior to Applicant’s filing, for how else would Applicant be able to refer to the sequences by said accession numbers. However, for completeness, two examples from table 2, noting only 1 is required, will be discussed for obviousness. As discussed above, the combined prior art references make obvious the use of a bacteriocin, such as one or more of the colicin E9’s of Walker et al, and its cognate immunity protein, such as the colicin E9 immunity protein of Uniprot. The prior art references, particularly UAB, Kwon et al, and University of Glasgow recite the use of paired colicin/klebicin/pyocin and its cognate immunity protein generically so as to suggest utility of and predictable success with using a wide array of such pairs as desired for the particular assay in which the support of UAB as modified by the additional prior art references is to function. From this generic teaching, the artisan would understand the predictability of and optimizable nature of altering/modifying the bacteriocin/immunity protein pair(s) on the support and would have found it obvious to look to the prior art for such pairs, particularly from pairs associated with gram negative infection such as the pairs taught by University of Glasgow to assay for gram negative infection to guide treatment.
The prior art teaches the sequence of VCW48573 (available at least as of 11/09/2018; a colicin E9) and a cognate immunity protein having the sequence of AAA23069 (available at least as of 07/23/2016; a colicin E9 immunity protein).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the combined references before the effective filing date of the claimed invention. The artisan would have been motivated to make the invention as claimed to assay for gram negative infection as taught by University of Glasgow. The artisan, given the generic disclosure of paired colicin/klebicin/pyocin and its cognate immunity protein, would have understood that the particular bacteriocin and/or cognate immunity protein would be predictably altered such that the VCW48573 (a colicin E9) and a cognate immunity protein having the sequence of AAA23069 (a colicin E9 immunity protein) would have been functionally equivalent to the colin E9 of Walker et al and the colicin E9 immunity protein of Uniprot. It is prima facie obvious to swap one known equivalent for another to achieve the same purpose, here, to swap one known E9 colicin for another and/or to swap one known colicin E9 cognate immunity protein for another (see MPEP sections 2143(I)(B) and 2144.06 (II)).The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Applicant’s Arguments and Responses
The rejections presented in the previous office action have been withdrawn and replaced with the rejections presented in this Office Action, which have been substantially altered to account for Applicant’s newly amended claim scope resulting from the 04/02/2026 claim amendments. The rejections presented in this Office Action are deemed to make obvious the claims as presently drafted.
Conclusion
Notice of Allowable Subject Matter:
Regarding claim 6, in light of the claim amendments clearly requiring 100% identity to the claimed sequence portions, the sequences as now claimed have been searched and are deemed to be free of the prior art. The closest prior art is University of Glasgow teaching SEQ ID NO: 23 at page 17 which differs from the claimed sequence of residues 255-390 of instant SEQ ID NO: 15 by a single amino acid. However, there is nothing in the prior art to motivate a mutation to this region of the E9 sequence and the prior art does not tech an identical sequence to that which is claimed. The art suggests that a single mutation can have a significant effect on the function(s) of a bacteriocin (see the cited teachings of Walker et al as cited in the rejections under 35 USC §103). Therefore, there is no reason to alter the prior art sequence of University of Glasgow and there would not be a reasonable expectation of success when doing so.
Regarding claim 9, it is noted that SEQ ID NOs: 1-27 are deemed to be free of the prior art for reasons noted in the office action dated 02/11/2025.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Note that the references and arguments/rationale cited by the International Search Authority in the Written Opinion for PCT/EP2019/081692 (as filed by Applicant in the instant Application) provide examples of peptides functionalized on supports for multiplex binding experiments wherein the peptides may be bacteriocins/cognate immunity proteins and are deemed relevant to the instant claims and disclosure.
Tighe et al (ELISA in the multiplex era: Potentials and pitfalls, PMCID: PMC6680274/ PMID: 25644123 [available 2015 Mar 25]) teach the advantages offered by multiplex versus single plex assays.
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 ASHLEY GAO whose telephone number is (571) 272-5695. The examiner can normally be reached on Monday- Friday 8-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
supervisor, Gregory Emch can be reached on (571) 272-8149. The fax phone number for the
organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent
Application Information Retrieval (PAIR) system. Status information for published applications
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applications is available through Private PAIR only. For more information about the PAIR
system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR
system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would
like assistance from a USPTO Customer Service Representative or access to the automated
information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
Prosecution Insights