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.
Claims 14-15 and 19-20 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected groups/inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/09/2024.
Claims 1-22 are pending.
Claims 21-22 are new.
Claims 1-13, 16-18, and 21-22 are under examination on the merits.
Withdrawn Objections and Rejections
In light of the clarifying and corrective amendments to the specification dated 07/10/2025, it is presumed the Applicant’s intended specification is that submitted on 05/14/2021 that is 53 pages in length, where the amendments noted in the remarks are deemed to address and overcome the objection to the specification for embedded browser-executable code. The rejection of claim 5 under 35 USC §112(a) is withdrawn in further consideration of the arguments contained in the remarks dated 07/10/2025 and in light of the teachings of Sharp et al (PLOS Computational Biology, 2017, htps://doi.orgl10.1371/journal.pcbi.1005652; see for example Figure 1 and its caption) as referenced in the instant specification at page 17, which are deemed to describe a structure-function correlation adequate to describe the sequences as claimed in instant claim 5 (see for example, the cited portions of Sharp et al). The rejections of claims 1 and 12 under 35 USC §112(b) are withdrawn in light of the claim amendments dated 07/10/2025. The rejections of the claims under 35 USC §§ 102 and 103 are withdrawn in light of the arguments made in the 07/10/2025 remarks and are replaced with the rejections under 35 USC §103 as presented in this Office Action to better account for the 07/10/2025 claim amendments.
Claim Interpretation
Note that a reasonable interpretation of claims reciting “has or contains a sequence of” would encompass and be anticipated/made obvious by a sequence comprising as little as 2 consecutive amino acids of the recited/claimed SEQ ID NOs. If this is not Applicant’s intent, Applicant is encouraged to amend the claims to employ more traditional claim language with a clear plain meaning such as amending the claim to use the following language: ‘comprise/comprises/comprising’ or ‘consist/consists/consisting of’, depending upon the scope Applicant intends to claim.
Note that instant claim 9 recites that the peptide ‘has a sequence selected from the group consisting of” the recited SEQ ID NOs and is being interpreted as requiring one of the full length SEQ ID NOs: 1-27 (not a fragment having 2 consecutive amino acids thereof).
Note the cognate binding partners of bacteriocins are also called cognate immunity proteins (see for example, pages 15 and 19 of the specification).
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).
Claim Objections
Claim 9 is 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.
Newly Necessitated-Claim Rejections
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) 1-4, 7-8, 10-13, 16, 18 and 21-22 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)) and University of Glasgow (WO 2016046218 A1).
Regarding claims 1-3, 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.
However, University of Glasgow teaches a bacteriocin (pyocin) which comprises a sequence identical to residues 255-390 of instantly claimed SEQ ID NO: 9 (see for example, page 17 and University of Glasgow’s SEQ ID NO: 23; taught to be the effector portion of pyocin AP41).
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 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/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. However, University of Glasgow teaches a pyocin (AP41) having the required structure of the bacteriocin of claim 6, which depends from claim 1. The artisan would have been motivated to adapt the assay to comprise the pyocin of University of Glasgow for two reasons. First, as mentioned above, the pyocin 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 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, where the bacteriocin of University of Glasgow comprises the required structure of claim 6, 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 had a reasonable expectation of success based on the cumulative disclosure of these prior art references.
Regarding claim 4, University of Glasgow teaches that S-type pyocins, klebicins and colicins have evolved to efficiently cross the gram-negative outer membrane through the parasitisation of existing active nutrient uptake pathways with cytotoxic activity most commonly taking the form of a nuclease activity targeting DNA, rRNA or tRNA, or a pore-forming activity. Pyocins Sl, S2, S3, and AP41 (the pyocin having the required structure of instant claim 6) display DNase activity, and the S-type pyocin (which includes AP41; see for example pages 4 and 8) may comprise a cytotoxic domain from a colicin (see for example, pages 2, 4, 6, 11, and 19).
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 University of Glasgow teach a pyocin (bacteriocin) comprising the structure required by claim 6 (exemplary of a pyocin of claim 1) and teach that this pyocin may comprise a cytotoxic domain. The artisan would have had a reasonable expectation of success based on the cumulative disclosure of these prior art references.
Regarding claims 7-8, UAB teaches multiple immunity protein polypeptides which may be immobilized on a support (see for example, claims 21-35 and 40 at pages 47-49 and page 2 including Figures 1A-c). Kwon et al teach means for using a support with immobilized proteins for an immunoassay (see for example, pages 157-158 and 160).
Kwon et al and UAB do not teach a specific immunity protein having a Kd of equal to or less than 10-10M for its cognate binding partner.
However, University of Glasgow teaches a polypeptide comprising a sequence identical to residues 333 to 421 of SEQ ID NO: 14, thereby meeting the limitations of instant claim 8 (see the claim interpretation section, above and see further, for example, University of Glasgow’s SEQ ID NO: 28 which is disclosed as the immunity protein partner of pyocin/bacteriocin AP41 at page 21).
It would have been prima facie obvious to practice the method of UAB as modified by Kwon et al and University of Glasgow for the reasons iterated above. The artisan would have had a reasonable expectation of success in functionalizing the immunity protein of University of Glasgow to a support as taught by UAB for an immunoassay as taught by Kwon et al. The artisan would have been motivated to do so in order to study or make use of said immunity protein for known uses such as treatment of respiratory infections as taught by University of Glasgow (see for example, page 40) where the immunity protein may be functionalized and used to screen for/isolate the pyocin of University of Glasgow which is taught to have therapeutic benefit (see for example pages 1-2 and 9). The immunity protein of University of Glasgow, having the required structure of claim 8 as presently drafted, which depends from and recites an exemplary immunity protein of claims 7 and 1, is presumed to have the recited properties (such as the recited Kd for its cognate binding partner) because 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. 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 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 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, 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 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, 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, UAB, Kwon et al, and University of Glasgow 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.
Claim(s) 5-6 and 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over UAB, Kwon et al, and University of Glasgow, as applied to claims 1-4, 7-8, 10-13, 16, 18, and 21-22 above, in further view of Walker et al (Nucleic Acid Research, 2002, 30(14), 3225-34; as cited on page 16 of the instant specification).
Regarding claim 5, UAB, Kwon et al, and University of Glasgow, while teaching claims 1-3, do not teach the sequence of instant SEQ ID NO: 29.
However, Walker et al teach that the H-N-H (ßßα-Me motif) of the cytotoxic domain of bacteriocins (such as colicin E9) 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).
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 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 had a reasonable expectation of success based on the cumulative disclosure of these prior art references.
Regarding claim 6, University of Glasgow teaches a bacteriocin (pyocin) which comprises a sequence identical to residues 255-390 of instantly claimed SEQ ID NO: 9 (see for example, SEQ ID NO: 23 at page 17; taught to be the effector portion of pyocin AP41).
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, Walker et al, and University of Glasgow. The artisan would have been motivated to conduct an assay comprising immobilizing the bacteriocin (pyocin) of University of Glasgow 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 bacteriocin for known uses such as studying treatment of respiratory infections as taught by University of Glasgow (see for example, page 40). The artisan would have had a reasonable expectation of success based on the cumulative disclosure of the prior art references.
Regarding claim 17, UAB, Kwon et al, and University of Glasgow teach the limitations of instant claim 4.
UAB, Kwon et al, and University of Glasgow do not teach that the cytotoxic domain of a bacteriocin may be mutated to deprive it of cytotoxic activity.
However, Walker et al teach that colicin E9 is a microbial toxin that kills bacteria through random degradation of chromosomal DNA. Within the active site of the cytotoxic endonuclease domain of colicin E9 (the E9 DNase) is a 32 amino acid motif found in the H-N-H group of homing endonucleases. Crystal structures of the E9 DNase have implicated several conserved residues of the H-N-H motif in the mechanism of DNA hydrolysis. Walker et al used mutagenesis to test the involvement of these key residues in colicin toxicity, metal ion binding and catalysis. Walker et al’s data show, for the first time, that the H-N-H motif is the site of DNA binding and that Mg2+-dependent cleavage of double-stranded DNA is responsible for bacterial cell death (see abstract and reference in its entirety). Walker et al further teach that the H-N-H (ßßα-Me motif) of the cytotoxic domain of bacteriocins (such as colicin E9) may be substituted with alanine (H to A substitution at positions 102 or 103) to prevent DNAse activity where upon 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 the reference where there one of ordinary skill in the art would have a desire to diminish/remove DNAse activity; see for example, pages 3225-3226 and 3228-3232 and figure 7).
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 to make use of the assay of UAB as modified by Kwon et al and University of Glasgow according to Walker et al, to have a cytotoxic domain with reduced DNase activity (the mechanism of the E9 domain, see for example the abstract of Walker et al). The artisan may have desired reduced DNAse activity in order to study the target bacteria without destroying them. The artisan would have had a reasonable expectation of success based on the cumulative disclosure of these prior art references.
Applicant’s Arguments and Responses
A. Applicant argues that the rejections of the claims over the prior art under 35 USC § 103 should be withdrawn because in the prior art, bacteriocins/Immunity proteins are disclosed for their biological activities, i.e., as therapeutic tools, and not as molecular adaptors.
Response: Applicant’s arguments predominantly focus on an unclaimed function/role of being molecular adaptors. This is unpersuasive. First, this role/function is not required by the claims as presently drafted. Second, where the claimed components are structurally indistinguishable from the prior art components (as they are here) and the prior art teaches use of the components in the same arrangement for the same purpose (multiplex binding experiments), the product which is anticipated/made obvious by the prior art is deemed to possess the characteristics and perform the functions of the claimed product. The combination of the prior art references set forth above teaches all of the required limitations of the claims. The MPEP provides that:
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP 2112(I) with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103,”
(see MPEP 2112(I)). 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)).
Therefore, this argument is not deemed to be sufficient to overcome the rejections of record.
Conclusion
Notice of Allowable Subject Matter:
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.
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/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678