CTNF 18/254,476 CTNF 98638 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Please note : The Examiner handling this application has changed and is now Amanda Zahorik in Art Unit 1636. Application Status This action is written in response to applicant’s correspondence received 03/19/2026. Claims 1-10, 15-22, 24 and 26 are currently pending. Claims 3, 7-10, 18-19, 21 and 26 are withdrawn from prosecution as being drawn to non-elected subject matter. Accordingly, claims 1-2, 4-6, 15-17, 20, 22 and 24 are examined herein. The restriction requirement mailed 01/21/2026 is still deemed proper. Election/Restrictions 08-25-01 AIA Applicant's election without traverse of the invention of Group I (claims 1-6, 15-22 and 24) and the species of: a truncation of the YjdB domain of autolysin (claim 17); a modification via introduction into a nucleic acid sequence encoding the autolysin (as recited in claim 4); a pip gene mutation (resistance to c2-type c2 phages) (claim 20); and species 16(c); in the reply filed on 03/19/2026 is acknowledged. Claims 3, 7-10, 18-19, 21 and 26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Objections to the Specification 06-16 AIA Applicant is reminded of the proper language and format for an abstract of the disclosure. The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided. In the instant case, the abstract contains the phrase “said modified strain”, which includes legal phraseology, “said”. Amending the abstract to remove the legal phraseology would obviate this objection. Objections to the Drawings 06-24-01 AIA Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification: The patent or application file contains at least one drawing executed in color (the supplemental drawings filed 05/25/2023). Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2). 07-30-03-h AIA Claim Interpretation Claim 1 recites a bacterial strain which has been modified to reduce the activity and/or expression of autolysin, wherein said modified strain has reduced sensitivity to bacteriophage. The broadest reasonable interpretation of the claim encompasses any strain of bacterium which has been modified in any way that has the effect of reducing the activity and/or expression of an autolysin. Per the instant specification, an autolysin is, “an endogenous lytic enzyme which breaks down the cell-wall peptidoglycan of the bacteria which produce them” (p. 10 ln 10-12). The term is not interpreted as encompassing phage and prophage enzymes, because while prophage enzymes may be produced by the host via expression of prophage genes which are integrated into the host genome, they are of phage origin and thus are not endogenous to the bacterium. Modifications which may reduce autolysin activity and/or expression include genetic modifications (e.g., genome editing, antisense inhibition) and chemical modifications (e.g., delivery of antibiotics or other small molecules which inhibit autolysin). The reduction of autolysin may be via direct targeting of the autolysin or indirect targeting via modulation of the expression and/or activity of a regulator of autolysin expression and/or activity. Please note that the claim does not state that the modification to reduce autolysin activity/expression causes the reduced sensitivity to bacteriophage. Instead, the broadest reasonable interpretation encompasses strains which have been modified to reduce autolysin activity/expression, and wherein (in which) other modifications are also present which reduce bacteriophage sensitivity. Contrast this language to the language in claim 5, which recites, “wherein said autolysin R allele reduces the sensitivity to phage D687”. That language is interpreted as requiring a causative relationship between the allele and the phenotype. Claim Rejections - 35 USC § 112(b) 07-30-02 AIA 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. 07-34-01 Claims 1-2, 4-6, 15, 17, 20, 22 and 24 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. Claim 1 is unclear over recitation of the term “activity and/or expression of autolysin”. This language is considered to be indefinite because the lack of “an” before “autolysin” suggests that the claim refers to a specific autolysin (e.g., the autolysin having an amino acid sequence as defined in SEQ ID NO: 2, as recited in claim 16), as opposed to the broad genus of autolysins. However, a search of the prior art did not show any species of autolysins which were unambiguously referred to as simply “autolysin”. It is noted that the specification states that “autolysin” refers to, “an endogenous lytic enzyme which breaks down the cell-wall peptidoglycan of the bacteria which produce them. Autolysins are classified as peptidoglycan hydrolases.” This would indicate that the term encompasses a genus, and is not limited to one particular species. However, because it is unclear from the phrasing of the claim whether “autolysin” refers to one specific autolysin or to the genus of autolysins as a whole, and these two interpretations are mutually exclusive, the metes and bounds of the claim are unclear. Amending the claim to recite “ an autolysin” would obviate this rejection. Claim 5 recites the term “autolysin R ”. However, neither the claim nor the specification defines a structure for that allele. Both only define the structure by its function of reducing sensitivity to phage D6867. The specification states, “The inventors have shown that certain autolysin alleles are able to reduce the sensitivity of Lactococcus lactis SL12699 to phage D6867 when they are inserted in lieu of the original (i.e. native) allele of the autolysin gene (SEQ ID NO:1) of SL12699. These alleles are defined herein as "autolysin R alleles". As a result, the metes and bounds of the claimed structure are unclear, particularly in combination with the indefiniteness of claim 1, described above. Claim 16 is excluded from the above rejections because it defines the allele relative to a specific sequence, SEQ ID NO: 2 and variants thereof, thus providing a broad but defined structure. Those claims identified in the statement of rejection but not explicitly referenced in the rejection are also rejected for depending from a rejected claim but failing to remedy the indefiniteness therein. Claim Rejections - 35 USC § 112(a) – Written Description 07-30-01 AIA The following is a quotation of the first paragraph of 35 U.S.C. 112(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. 07-31-01 AIA Claim s 1-2, 4-6, 15-17, 20, 22, and 24 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”. For claims drawn to a genus, MPEP § 2163 states the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly , 119 F.3d at 1568, 43 USPQ2d at 1406. Claim 1 is drawn to a generic bacterial strain which has been modified to reduce the activity and/or expression of what is interpreted to be a generic autolysin. This strain also has reduced sensitivity to a generic bacteriophage, to any degree. Claim 2 recites that the modification renders the autolysin partially or completely non-functional, but does not limit the strain, autolysin or bacteriophage. Claim 4 specifies that the modification has been introduced into the (elected species of) a nucleotide acid sequence which encodes said autolysin, or in to a regulatory region controlling the autolysin, but does not limit the strain, autolysin or bacteriophage. Claim 5 recites that the strain has been modified to comprise an autolyinR allele, but that term is indefinite, as described above. The remaining limitations do not limit the structure of the autolysin, but merely recite functional characteristics. Nor does the claim limit the strain or bacteriophage. Claim 6 recites wherein the strain is homozygous for the modification, but does not limit the generic elements of claim 1. Claims 15-17, 20, 22 and 24 likewise recite various functional characteristics and additional structural characteristics such as additional modifications, and claim 22 limits the bacterial strain to a lactic acid strain, but otherwise do not limit the strain, autolysin or bacteriophage. In contrast to the broad genera of bacteria, autolysins, modifications and bacteriophages recited by the claims, the specification exemplifies one specific phase resistant strain of Lactococcus lactis SL12852, with mutations in a specific autolysin gene which result in a truncated protein. On page 40, the specification describes the creation of phage-resistant strain SL12852 (DGCC12852) during phage challenge using parental strain SL12699 and P335-like phage D6867. On pages 10 and 11, the specification states that the nucleotide sequence which encodes the parental autolysin is SEQ ID NO: 1, and its amino acid sequence is SEQ ID NO: 2. On page 40, the specification identifies a 155-bp deletion in autolysin, relative to the gene in the parental strain, as essential for the functional limitation of phage resistance (p. 40 ln 15-28). On page 15, the specification states that, in a preferred aspect, the deletion is about a 153 nucleotide deletion starting at position 1,225 of SEQ ID NO: 1. Sanger sequencing showed that there were other variant mutations which caused premature stop codons, but all were located in the yjdB domain and all led to a truncated autolysin protein. Figure 1 depicts the three variants. Therefore, the specification discloses a correlation between the recited functions (reducing activity/expression of autolysin and phage resistance) and a specific deletion of the yjdB domain of a specific autolysin gene in a specific L. lactis strain. The genus of bacteria is vast, encompassing all bacterial species. Within that genus, the structure and function of autolysins is correspondingly large and varied, and the correlation between autolysin structure and phage resistance is not well-understood. Regarding autolysins in general, the genus displays significant variability in structure and function, and is relatively understudied. Mitchell notes that, “Autolysins have not been as extensively studied as other lysins” (Mitchell et al. Building blocks and blueprints for bacterial autolysins. PLoS Comput Biol. 2021 Apr 1;17(4):e1008889.)(p. 2). Insofar as lysins – both endo- and autolysins – have been studied, they display significant differences in their architecture and target specificity. Mitchell states, “In some cases, a catalytic domain (CAT) handles both recognition and digestion, while in other cases, a lysin also includes one or more cell wall binding domains (CWB) to specifically recognize peptidoglycan. Different CATs attack different peptidoglycan bonds in different contexts; e.g., Mur-NAc-LAAs target a bond in the stem peptide, N-acetylmuramidases cleave the glycan backbone, and peptidases digest amino acid bonds…Likewise, different CWBs have different recognition specificities; e.g., CW_binding_1 shows affinity for cell walls containing choline…while LysM is quite diverse but generally recognizes N-acetylglucosamine…Finally, there is significant diversity in lysin architectures, i.e., how CATs and CWBs are integrated in a single enzyme to work together in attacking peptidoglycan.” ( Id .). It is noted that while Mitchell writes shortly after the filing date of the instant invention, Mitchell’s disclosures are provided to illustrate a scientific truism, which is the variability of autolysin structure, and to show that even after the filing date, autolysins had not been well-studied. Regarding bacteriophages in general, even when confined to lactic acid bacteria, phage diversity and phage-host specificity are variable in both structure and function. Martínez notes, “The host range of LAB phages is, in general, highly specific and in some cases, phages infecting particular strains within a bacterial species are isolated.” (Martínez et al. Cell wall homeostasis in lactic acid bacteria: threats and defences. FEMS Microbiology Reviews, fuaa021, 44, 2020, 538–564. )(p. 547). Martínez indicates that biochemical diversity of the cell wall polysaccharides of lactic acid bacteria (LAB) species explains the narrow host range of LAB phages (p. 548). Regarding the correlations among host bacteria, autolysins and phage resistance, what little is known about the connection between autolysin structure and phage resistance has mostly been demonstrated in Staphylococcus aureus. Fernández found that, in that species, “deletion of atl led to low-level resistance to CHAPSH3b and the endolysin LysH5” (Abstract)(Fernández et al. Downregulation of Autolysin-Encoding Genes by Phage-Derived Lytic Proteins Inhibits Biofilm Formation in Staphylococcus aureus. Antimicrob Agents Chemother. 2017 Apr 24;61(5):e02724-16.). LysH5 is, “derived from phage vB_SauS-philPLA88” (p. 2, Id .). However, they also note that, “To our knowledge, this would make atlA the first known phage lysin resistance determinant.” (p. 9). This suggests that, by 2017, very little was known about the correlation between bacterial genes and phage lysin resistance. They suggest that, “attaining a better understanding of bacterial responses to nonlethal antimicrobial concentrations may provide hints about mutations that lead to resistance”, but note that identifying the correlation between these possible mutations and phage resistance is significantly challenging, stating, “In the case of phage-derived lytic proteins, our results show that mutational resistance is possible but that the increase may be so small that these mutants would be difficult to identify in routine screenings. This would explain why no resistant strains have been generally isolated after rounds of exposure to phage lytic proteins.” (p. 9, Id .). They also indicate that these results vary depending on the phage lysin, stating, “our results show that the atl mutant displays a greater increase in resistance to LysH5 than to CHAPSH3b compared to the parental and complemented strains. Thus, depending on their specific targets in the PG or their binding sites, some lytic proteins may be more affected by lower expression or mutation of autolysin genes.”. This indicates that the impact of autolysin mutation on phage resistance can be highly variable, and points away from a consistent, art-recognized correlation between autolysin structure and phage resistance. In summary, in contrast to the breadth of the claims and the narrow embodiments disclosed by the specification, the state of the art shows a significant amount of variability and unpredictability within the genera of the claimed bacteria, autolysins and phages. Based on the breadth of the claims, the limited amount of guidance provided by the specification and the art, the high degree of variation among members of the claimed genus, and further the unpredictability in the art, one of ordinary skill in the art would conclude that Applicant was not in possession of the invention as broadly claimed. Claim Rejections - 35 USC § 112(a) – Deposit Rules 07-31-02 AIA Claim s 5 and 16 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention. The specification lacks complete deposit information for the deposit of phage D6867 (DSM 33596) and Lactococcus lactis ssp. Lactis SL12699 (DSM 3360). Claim 5 recites phage D6867 and a derivative strain of Lactococcus lactis SL12699. The specification states that phage D6867 is available at the Leibniz Institution DSMZ-German Collection of Microorganisms and Cell Cultures under accession number DSM 33596. The host strain of that phage, and the strain from which the instantly claimed strain is derived, is available under accession number DSM 3360. The specification discloses that L. lactis SL12852 (DGCC12852) was created via phage challenge using parental strain SL12699 (p. 40 ln 17-19). The mutation responsible for the phage resistance was initially unknown, but was identified as a 155-bp deletion in an autolysin gene (p. 40 ln 20-22) after comparison of the two genomes. The autolysin gene in the parental strain is disclosed to be SEQ ID NO: 1, per the sequence listing and p. 13 ln 6-10). The specification further discloses that, in a preferred aspect, the deletion corresponds to about a 153 nucleotide deletion starting at position 1,225 of the autolysin gene encoded by SEQ ID NO: 1 (p. 14 ln 1-2). Because the claimed bacterial strain was derived from the parental strain SL12699, and the mutation is relative to that strain’s autolysin gene as represented by SEQ ID NO: 1, at least that parental strain is required to make and use the invention. Furthermore, the claim requires the functional characteristic of sensitivity to phage D6867 as determined by EOP Assay I. To conduct that assay, phage D6867 would be required. Based on the above, it is not clear that the invention will work with commonly available material and it is not apparent if the biological materials considered necessary to make and use the invention is both known and readily available to the public. As such, the biological material must be known and readily available or obtainable by a repeatable method set forth in the specification, or otherwise known and readily available to the public. If it is not so obtainable or available, the requirements of 35 USC 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, may be satisfied by a deposit of the strains . Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action: A person shall be entitled to a patent unless – 07-08-aia AIA (a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention. 07-12-aia AIA (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. 07-15 AIA Claim s 1-2 and 4 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Lubitz (Lubitz et al. Requirement for a Functional Host Cell Autolytic Enzyme System for Lysis of Escherichia coli by Bacteriophage XX174. JOURNAL OF BACTERIOLOGY, July 1984, p. 385-387.) . Regarding claim 1, Lubitz teaches a modified E. coli (“temperature sensitive mutant”) which has been modified for reduced autolysin expression/activity (“defective in autolysis”) and which has reduced sensitivity to bacteriophage (infection does not cause host cell lysis) (Abstract). The strain carried a temperature-sensitive mutation in the lytA gene, wherein the lytA gene is active at 30°C but inactive at 42°C (p. 385). Lubitz further shows that, “ induction of the cloned ɸX174 gene E with isopropyl-o-D-thiogalactoside resulted in lysis at 30°C but not at 42°C.” and concludes that “host cell lysis by phage ɸX174 is dependent on a functional cellular autolytic enzyme system” (Abstract). Regarding claim 2, Lubitz teaches that the autolysin is completely non-functional with respect to (i.e., in the context of) phage infection (see above). Regarding claim 4, Lubitz teaches that the modification has been introduced into a nucleic acid sequence which encodes autolysin (mutation in the lytA gene; see above) . Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-23-aia AIA The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows: Determining the scope and contents of the prior art. Ascertaining the differences between the prior art and the claims at issue. Resolving the level of ordinary skill in the pertinent art. Considering objective evidence present in the application indicating obviousness or nonobviousness. 07-20-02-aia AIA 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. 07-21-aia AIA Claim s 1-2, 4, 22 and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Dupont (Identification of Lactoccus lactis Genes Required for Bacteriophage Adsorption. APPLIED AND ENVIRONMENTAL MICROBIOLOGY, Oct. 2004, p. 5825–5832.) in view of Lortal (Lortal et al. Role, mechanisms and control of lactic acid bacteria lysis in cheese. International Dairy Journal 15 (2005) 857–871.) Regarding claim 1, Dupont provides a teaching, suggestion or motivation to construct phage-resistant strains of L. lactis, because, “Lactococcus lactis is widely used in starter cultures for cheese production. Bacteriophage contamination during the fermentation process is a major problem, causing lysis of the starter bacteria and consequently slow or failed fermentation of the milk.”. Dupont further identified several target genes in strains which were resistant to phage infection (Abstract): Random insertional mutagenesis of the two L. lactis strains was carried out with the vector pGh9:ISS1, and integrants that were resistant to phage infection and showed reduced phage adsorption were selected. In L. lactis IL1403 integration was obtained in the ycaG and rgpE genes, whereas in L. lactis Wg2 integration was obtained in two genes homologous to ycbC and ycbB of L. lactis IL1403 . Dupont does not teach that the strain comprises a modification reduces autolysin activity or expression. Lortal is analogous to Dupont in that they discuss the importance of lactic acid bacteria in cheese production, particularly L. lactis , and discuss ways to optimize strains of the bacterium for improved production. One of these approaches is to control lysis by constructing genetically modified strains with inducible lysis, such as, “placing a gene (encoding the major AcmA autolysin or a phage endolysin) under the control of an inducible promoter” (p. 865 § 4). This approach, “was tested and shown to be efficient in cheese” ( Id .). It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the phage-resistant strain of L. lactis , as taught by Dupont, by placing the autolysin under the control of an inducible promoter, as taught by Lortal. The prior art teaches that L. lactis is an industrially significant bacterial strain, and that both phage resistance and controllable lysis are desirable traits in an industrial strain. The ordinary artisan would have been motivated to combine the references to produce a strain with those characteristics, and would have had a reasonable expectation of success based on the teachings of the prior art, which show that both characteristics had been successfully engineered in L. lactis. Regarding claim 2, Lortal teaches that the inducible promoter renders the autolysin at least partially non-functional. The term “with respect to phage infection” is not entirely clear, but is interpreted as meaning that the reduction of autolysin activity/expression can occur during phage infection. Given that the expression is inducible at any time, it is considered inducible with or without respect to phage infection. Regarding claim 4, Lortal teaches wherein the modification has been introduced into a regulatory region which contributes to controlling the expression of the autolysin (see above). Regarding claim 22, both references teach that the strain is a lactic acid strain (see above). Regarding claim 24, both references teach foods (cheese) comprising L. lactis (see above) . 07-21-aia AIA Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Dupont and Lortal, as applied to claims 1, 2, 4, 22 and 24, further in view of Millen (Millen et al. Genetic determinants of lactococcal C2viruses for host infection and their role in phage evolution. J Gen Virol. 2016 Aug;97(8):1998–2007.) . Dupont and Lortal render obvious the invention of claim 20, from which instantly rejected claim 20 depends, as described above. Dupont and Lortal do not teach wherein the strain is additionally mutated in its pip gene and resistant to c2-type c2 phages. Millen teaches a c2-type bacteriophage-insensitive mutant, L. lactis DGCC11032, with a mutation in pip (Abstract). It would have been prima facie obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to have modified the strain as taught by Dupont and Lortal to further comprise additional bacteriophage resistance by mutating the pip gene, as taught by Millen, to predictably yield an industrially-relevant L. lactis strain with additional resistance to phage contaminants. Subject Matter Free of the Prior Art The following subject matter is free of the prior art: The prior art does not teach or suggest a L. lactis SL12852 strain with mutated autolysin gene, the gene comprising a nucleotide sequence which is a variant of SEQ ID NO: 1 in which the YhdB has been deleted, wherein the strain has increased resistance to P335-like phage D6867. The closest prior art is Fernández (cited above), which discloses a phage-resistant S. aureus strain in which the autolysin gene, atlA, has been deleted, as described in the above rejection of the claims under 35 U.S.C. 112(a). However, the prior art discloses a distinct species of bacteria with a different gene and different phage susceptibilities. As discussed in the same rejection above, there is significant interspecies variability and unpredictability in autolysin structure and function and phage susceptibility, and little was known about the correlations between them. This would have made it difficult to reliably extrapolate the results seen in S. aureus to other species of bacteria and their associated phages, with any degree of predictability. As a result, the ordinary artisan would not have been able to predict, with a reasonable expectation of success, that particular truncation of the specifically disclosed autolysin gene in the specifically disclosed strain of L. lactis would have yielded resistance to the specifically disclosed bacteriophage. Frias et al. (cited by applicant on an IDS) also teaches that deletion of the autolysin lytA in Streptococcus pneumoniae was required for efficient bacteriophage progeny release (Title). However, this is again a distinct bacterial species and gene, and given the variability and unpredictability of the art, as already described, the ordinary artisan would not have reasonably been able to predict that deletion of the specifically disclosed L. lactis autolysin would have led to the specifically disclosed phage resistant phenotype. Conclusion No claim is allowed at this time. Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA M ZAHORIK whose telephone number is (703)756-1433. The examiner can normally be reached M-F 8:00-16:00 EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached on (571) 270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. 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If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /AMANDA M ZAHORIK/Examiner, Art Unit 1636 Application/Control Number: 18/254,476 Page 2 Art Unit: 1636 Application/Control Number: 18/254,476 Page 3 Art Unit: 1636 Application/Control Number: 18/254,476 Page 4 Art Unit: 1636 Application/Control Number: 18/254,476 Page 5 Art Unit: 1636 Application/Control Number: 18/254,476 Page 6 Art Unit: 1636 Application/Control Number: 18/254,476 Page 7 Art Unit: 1636 Application/Control Number: 18/254,476 Page 8 Art Unit: 1636 Application/Control Number: 18/254,476 Page 9 Art Unit: 1636 Application/Control Number: 18/254,476 Page 10 Art Unit: 1636 Application/Control Number: 18/254,476 Page 11 Art Unit: 1636 Application/Control Number: 18/254,476 Page 12 Art Unit: 1636 Application/Control Number: 18/254,476 Page 13 Art Unit: 1636 Application/Control Number: 18/254,476 Page 14 Art Unit: 1636 Application/Control Number: 18/254,476 Page 15 Art Unit: 1636 Application/Control Number: 18/254,476 Page 16 Art Unit: 1636 Application/Control Number: 18/254,476 Page 17 Art Unit: 1636 Application/Control Number: 18/254,476 Page 18 Art Unit: 1636 Application/Control Number: 18/254,476 Page 19 Art Unit: 1636 Application/Control Number: 18/254,476 Page 20 Art Unit: 1636
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