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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 19, 2026 has been entered.
Application Status
This action is written in response to applicant’s correspondence received May 19, 2026. Claims 1, 5-7, 12-17, 19-23 and 27-30 are presented in claims filed on May 19, 2026. Claims 5, and 28-30 are withdrawn from nonelected inventions. Accordingly, claims 1, 6-7, 12-17, 19-23, and 27 are currently pending and under examination.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Claims 1, 6, 7, 12-17, 19-23, and 27 for foreign priority to EPO 20172078.6, filed on 29 Apr 2020, is acknowledged. Support for instantly amended limitation in claim 1 can be found in disclosure "in an embodiment, step b) of the method of the invention is the replacement of the intergenic region between the galR and the galK genes of the gal-lac gene cluster of the Streptococcus thermophilus strain provided in step a) by the sequence as defined in SEQ ID NO: 2 or a SEQ ID NO: 2 derivative (i.e., there is no other modification of the gal-lac gene cluster than the replacement by SEQ ID NO: 2 or the SEQ ID NO: 2 derivative) (pg. 12, lines 4-9).
Claim Objections
Claim 1 objected to because of the following informalities: in lines 5 and 6, the recitation of “galR-galK intergenic region” and “galK coding sequence” includes names of genes which needs to be written in italics. Appropriate correction is required.
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.
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.
Claims 1, 6, 7, 12, and 19-23 are rejected under 35 U.S.C. 103 as being unpatentable over Vaillancourt (Appl. Environ. Microbiol. (2004), 70, 8, 4596-4603; DOI: 10.1128/AEM.70.8.4596–4603.2004.) in view of Vaughan (Activation of Silent gal Genes in the lac-gal Regulon of Streptococcus thermophilus; Journal of Bacteriology, 2001, 183(4):1184-1194) and de Vin (IDS Received Date: 05/14/2025; Cite No. 1; Appl. Environ. Microbiol. (2005), 71, 7, 3659-3667; DOI: 10.1128/AEM.71.7.3659–3667.2005).
Regarding claim 1, Vaillancourt teaches a method for generating a S. thermophilus strain capable of utilizing galactose for growth (e.g., Gal+ strain) via complementation or recombination with galK gene from S. salivarius, a phylogenetically related Gal+ species (pg. 4597, col. 1, para. 3). Vaillancourt further teaches the complemented galK gene also comprises its own ribosome binding site and the promoter region of the gal operon without the binding site of GalR (pg. 4597, col. 2, para. 2), and the resulting recombinant S. thermophilus SMQ-301K01 Gal+ strain comprises an intact gal locus in the chromosome(pg. 4597, col. 2, para. 3). Vaillancourt further teaches that complementation led to improved galactokinase activity in SMQ-301K01, confirming Gal+ phenotype (pg. 4598, col. 1, para. 2; pg. 4601, col. 1, para. 1).
Although Vaillancourt teaches the S. thermophilus Gal+ strain comprises a modification of the native galR-galK intergenic region, Vaillancourt does not teach that the galK coding sequence is not replaced.
Vaughan teaches Streptococcus thermophilus strain CNRZ 302 is unable to ferment galactose (e.g., a Gal- strain) and it contains structurally intact galKTE genes organized into a gal operon, but these gal genes are poorly transcribed (abstract; Fig. 2), essentially no clear signal for the galK gene is detected (pg. 1189, col. 1, para. 1). Vaughan further teaches nine Gal+ strains contain point mutations in the galK promoter within the galR and galK intergenic region, specifically an extra A residue inserted in a stretch of adenines preceding the -35 region, a G-to-T substitution 3 bp preceding the -10 box, and a G-to-A substitution in the -10 box (Fig. 4A; pg. 1192, col. 1, para. 1). Further, Vaughan demonstrates the galactokinase activity expressed from mutated promoters enables Gal+ phenotype compared to S. thermophilus Gal-strains conferring wild-type promoters (pg. 1192, col. 1, para. 2). Vaughan states “it is likely that the basal GalK activity has increased in the mutant strains due to promoter-up mutations, which allows sufficient expression of the galK gene on induction for galactose utilization” (pg. 1192, col. 1, para. 2). In addition, Vaughan introduces galK-mutated promoter into a reporter plasmid, followed by transformation in S. thermophilus Gal-strain, and observes strong activity of the galK-mutated promoter capable of expressing downstream gene and enabling S. themophilus Gal-strain to consume both sucrose and lactose compared to Gal-strain transformed with wild-type galK promoter (pg. 1192, paragraph bridging col. 1 and 2). Thus, Vaughan demonstrates galK-mutated promoters are active and can be introduced in S. thermophilus Gal-strains to engineer strains with desirable activity.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified the method of Vaillancourt to engineer S. thermophilus Gal+ strains (i.e., exhibiting high galactose utilization profile) via complementation with functional galK-mutated promoters as taught by Vaughan because it would have merely amounted to applying a known technique to a known product ready for improvement to yield predictable results. It would have been obvious to one to have modified the native galR-galK intergenic region without replacement of the galK coding sequence as Gal- phenotype arises from inactive wild-type galK promoters lacking “promoter-up mutations” and not enabling transcription of the galK gene, rather than defective galK coding sequences as taught by Vaughan (pg. 1192, col. 1, para. 2; pg. 1189, col. 1, para. 1; pg. 2001, col. 1, para. 1; Fig. 3A). One would have had a reasonable expectation of success in doing so because Vaillancourt already teaches a method of engineering S. thermophilus Gal+ strains via complementation of galK gene comprising its own ribosome binding site and promoter region. Thus, Vaillancourt already demonstrates complementation of wild-type promoter in S. thermophilus Gal- strain with a mutated promoter from S. salivarius that contains two nucleotide mutations in the ribosome binding site as taught by Vaillancourt (pg. 4597, col. 1, para. 2), and the engineered S. thermophilus Gal- strain exhibits Gal+ phenotype.
However, Vaillancourt or Vaughan does not teach introducing a nucleic acid sequence comprising SEQ ID NO:2 or its derivative.
de Vin teaches the S. thermophilus EU20 (IMDOST40) strain carries a 141 bp long galR-galK intergenic region, which is the same as the instant SEQ ID NO: 2, with one key nucleotide substitution (T to G) in its Shine-Dalgarno sequence (pg. 3664, left-column, first paragraph). de Vin further teaches that this nucleotide substitution yielded a frameshift affecting the amino acid sequence of GalR after position 58 (pg. 3664, left-column, second paragraph), and EU20 had 11 amino acid differences in GalK and 13 amino acid differences in GalT (Table 5). Therefore, this nucleotide mutation correlates with the increased galactose-consumption rate and ability to consume the glucose and galactose moieties of lactose simultaneously (pg. 3662, right-column, second paragraph). de Vin further demonstrates that IMDOST40 “did not excrete galactose during growth on lactose and consumed the glucose and galactose moieties of lactose simultaneously” (pg. 3662, right column, second paragraph).
Following the obviousness to modify Vaillancourt’s method to introduce galK-mutated promoters in S. thermophilus Gal- strains without replacing the galK gene, it would have also been obvious to one of ordinary skill in the art before the effective filling date of the invention to have introduced another functional galK-mutated promoter, specifically SEQ ID NO: 2 as taught by de Vin because it would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. Based on the teachings of Vaughan that Gal- phenotype arises from inactive wild-type galK promoters lacking “promoter-up mutations” and not enabling transcription of the galK gene, rather than defective galK coding sequences as taught by Vaughan (pg. 1192, col. 1, para. 2; pg. 1189, col. 1, para. 1; pg. 2001, col. 1, para. 1; Fig. 3A), it would have been obvious to one to apply de Vin’s SEQ ID NO: 2 to a S. thermophilus Gal- strain via Vaillancourt’s known complementation technique as it would have merely amounted to applying a known technique to a known device ready for improvement to yield predictable results. One would have been motivated to have done so for the advantage of increasing galactose-consumption rate and consuming the glucose and galactose moieties of lactose simultaneously as taught by de Vin (pg. 3662, right-column, second paragraph), especially in applications involving dairy products to prevent undesirable accumulation of galactose in milk. One would have had a reasonable expectation of success in doing so because Vaillancourt teaches a method of generating recombinant S. thermophilus strain by replacement of native galK-wild-type promoter with galK-mutated promoter from a Gal+ strain, selection of Gal+ cells, and measurement of galactose consumption.
Regarding claim 6, the obviousness of improving S. thermophilus Gal- strain to Gal+ by modifying the native galR-galK intergenic region with SEQ ID NO: 2 of de Vin is discussed above as applied to claim 1.
Regarding claim 7, an ABSS search indicated that SEQ ID NOs: 3 and 4 align 100% with the EU20 Lelior gene cluster (IDS Received Date: 05/14/2025; Cite No. 6; NCBI Accession Number: AY704367; Version: AY704367.1; Pub Date: 08 Jul 2005). SEQ ID NO: 2 aligns base pairs 1085-1225; SEQ ID NO: 3 aligns to base pairs 891-1225; SEQ ID NO: 4, which encodes for transcriptional activator of the gal operon, aligns to base pairs 90-1225. It is noted that SEQ ID NO: 4 comprises SEQ ID NO:3, which then comprises SEQ ID NO:2. In addition, the gal operon of EU20 is annotated to be immediately downstream from base pairs 1226-4924. Therefore, it evident that SEQ ID NO:4 serves as the gal promoter. Vaillancourt teaches (pg. 4597, under section Construction of a galactose-positive recombinant strain of S. thermophilus) the DNA fragment (1,270 bp) used for recombination comprised of “the entire galK gene with its own ribosome binding site, as well as the promoter region of the gal operon”. Therefore, the obviousness of improving S. thermophilus Gal- cells to Gal+ cells by modifying the native galR-galK intergenic region with galK-mutated promoter (SEQ ID NO: 2) of de Vin including additional features encoded by SEQ ID NOs 3 and 4 as discussed above in claim 1 also applies here.
Regarding claim 12, it is recited that the strain obtained is not the S. thermophilus DSM32823 strain deposited at DSMZ on May 29th, 2018. The specification teaches that EU20 was originally part of the Rhodia Food Collection and later deposited as DSM32823 by DuPont Nutrition Biosciences ApS (pg. 2, lines 31-36). The recombination technique involves introducing SEQ ID NO:2 (a 141 bp fragment) of the EU20 gal promoter into a different host S. thermophilus strain SMQ-301, which would not render the resulting recombinant strain identical to EU20 as a whole. Accordingly, the resulting strain would not inherently be EU20 since the replacement of a promoter fragment does not convert the whole genome of SMQ-301 into EU20.
Regarding claim 19, the obviousness to modify Vaillancourt’s S. thermophilus Gal- strain to incorporate SEQ ID NO: 2 is discussed above as applied to claim 1. Although Vaillancourt and de Vin quantify galactose utilization using different measuring units than percentage of consumed galactose at the end of lactose consumption (VoLach), the difference in measurement units merely reflects a quantitative expression of an inherent characteristic of the recombinant strain resulting from the use of SEQ ID NO:2. The specification disclosed S thermophilus strains “were grown in conditions inspired from de Vin” (pg. 59, lines 33), and de Vin teaches that “during growth on lactose, there was no galactose accumulation detected in the medium for strain IMPOST40” (EU20) (pg. 3666, left-column, first sentence of second paragraph). This positively teaches that galactose in the media was consumed by EU20. Accordingly, one of ordinary skill in the art would have reasonably expected the substitution of the defective gal promoter of SMQ-301 with SEQ ID NO:2 and growing the recombinant cells under the same conditions would inherently yield a strain exhibiting the same known functional characteristics, including a VoLach percentage of at least 70%. Thus, the teachings of Vaillancourt and de Vin meets the claim limitation wherein the galactose utilization profile is further defined by a percentage of VoLach of at least 70%.
Regarding claims 20 and 21, the obviousness of inheriting functional properties VoLach and VmaxLach is discussed above as applied to claim 19. In addition, it would be obvious to one of ordinary skill in the art that a recombinant strain possessing SEQ ID NO: 2, which inherently exhibits each of the individual VmaxLach and VoLach characteristics would likewise exhibit both properties simultaneously.
Regarding claim 22, de Vin teaches additional seven strains besides EU20 displaying high galactose-utilization profiles and consuming all of the excreted galactose within 8.5h of fermentation (pg. 3662, right-column, second paragraph). de Vin further teaches that sequence alignment of these seven intergenic regions with SEQ ID NO: 2 of EU20 showed eight different nucleotide sequences (referred as NS1 to NS8) were found in the intergenic region: five strains contained two different nucleotide sequences (NS2), one strain was NS1, one strain was NS6, and EU20 was NS3 (Fig 2, Fig. 3, Table 4). It would be obvious to one of ordinary skill in the art to improve SMQ301 Gal- strain with one of these seven SEQ ID NO: 2 derivatives. The obviousness as discussed above in claim 1 applies here.
Regarding claim 23, the rationale is discussed above in claim 12 where recombination of a promoter fragment from EU20 into a different host strain SMQ301 would not inherently be EU20, which satisfies with the structural limitation “wherein genome sequence of the strain has an identity which is at most 99.98% to the genome sequence of the DSM32823 strain” (EU20).
Claims 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over Vaillancourt (Appl. Environ. Microbiol. (2004), 70, 8, 4596-4603; DOI: 10.1128/AEM.70.8.4596–4603.2004.) in view of de Vin (IDS Received Date: 05/14/2025; Cite No. 1; Appl. Environ. Microbiol. (2005), 71, 7, 3659-3667; DOI:10.1128/AEM.71.7.3659–3667.2005).
Regarding claim 13, the teachings of Vaillancourt’s S. thermophilus Gal+ strain generated via complementation with its galK gnee along with its own ribosome binding site and promoter region of the gal operon with functional heterologous galK promoter are discussed above as applied to claim 1.
In addition, the teachings of de Vin regarding a functional galR-galK intergenic region comprising instantly claimed SEQ ID NO: 2 and S. thermophilus Gal+ strains comprising this sequence are discussed above as applied to claim 1.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified Vaillancourt’s S. thermophilus Gal- strain with a functional galR-galK intergenic region (e.g., SEQ ID NO: 2) because it would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. Each substituted component (Vaillancourt’s Gal- strain galK promoter and de Vin’s SEQ ID NO: 2) and its functions were known in the prior art. One would have been motivated to have done so for the advantage of increasing galactose-consumption rate and consuming the glucose and galactose moiety of lactose simultaneously, especially in applications involving dairy products to prevent undesirable accumulation of galactose in milk as taught by de Vin (pg. 3662, col.2, para. 2). One would have had a reasonable expectation of success in doing so because Vaillancourt teaches recombinant S. thermophilus Gal- strains exhibiting Gal+ phenotype after complementation with functional galK promoter.
Further, Vaillancourt teaches S. thermophilus naturally possess a gal operon comprising genes that code for the enzymes of the Leloir pathway, namely galK, galT, and galE, which is immediately followed by galM and the lac operon comprising genes that encode for lacS and lacZ (pg. 4596, col. 2, para. 3). Thus, the complementation of introducing SEQ ID NO: 2 into S. thermophilus Gal- strain SMQ-301 would render a strain having a sequence of its gal-lac gene cluster comprising SEQ ID NO: 2. Further, the complementation involves introducing SEQ ID NO:2 (a 141 bp fragment) of the EU20 gal promoter into a different host S. thermophilus strain SMQ-301, which would not render the resulting recombinant strain identical to EU20 as a whole. Accordingly, the resulting strain would not inherently be EU20 since the replacement of a promoter fragment does not convert the whole genome of SMQ-301 into EU20.
Regarding claim 14, the teachings of SEQ ID NO:3 and SEQ ID NO: 4 are discussed above as applied to claim 7, and the obviousness of a recombinant S. thermophilus strain with its gal-lac gene cluster comprising SEQ ID NO: 2 discussed above as applied to claim 13 equally applies here.
Regarding claim 15 and 16, an ABSS search indicated that SEQ ID NO: 2 is encoded by SEQ ID NOs: 5 and 6 in the EU20 Leloir gene cluster. SEQ ID NO: 5 aligns to base pairs 478-1923 encoding part of the gal operon. SEQ ID NO: 6 aligns to base pairs 90-6040 which encodes for i) the gal operon including the gal promoter genes that code for enzymes of the Leloir pathway, namely, galactokinase (galK), galactose-1-phosphate uridylyltransferase (galT), and UDP-glucose 4-epimerase (galE) and ii) galactose mutarotase (galM).
Further, the teachings of Vaillancourt on generating a S. thermophilus Gal+ strain via complementation with functional heterologous galK gene along with its own ribosome binding site and promoter region, and teachings of de Vin on galR-galK intergenic region (i.e., SEQ ID NO: 2) that confers Gal+ phenotype are discussed above as applied to claim 13.
The obviousness to modify the S. thermophilus Gal- strain of Vaillancourt via complementation with a functional galR-galK intergenic region comprising SEQ ID NO: 2 is discussed above as applied to claim 13. It would have also been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified Vaillancourt’s S. thermosphilus Gal- strain via complementation of known functional gal operon comprising SEQ ID NO: 5 or SEQ ID NO: 6 because it would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. Each substituted component and its functions were known in the prior art. SEQ ID NO: 5 and SEQ ID NO: 6 are known naturally occurring gal operon comprising functional galR-galK intergenic region of SEQ ID NO: 2. Thus, complementation with known functional gal operon is an obvious design choice. One would have been motivated in doing so for the advantage of preserving native promoter and operon organizations. One would have had a reasonable expectation of success in doing so because de Vin teaches a S. thermophilus strain comprising a gal-lac gene cluster comprising SEQ ID NO: 5 and SEQ ID NO: 6.
Claim17 is rejected under 35 U.S.C. 103 as being unpatentable over Vaillancourt (Appl. Environ. Microbiol. (2004), 70, 8, 4596-4603; DOI: 10.1128/AEM.70.8.4596–4603.2004.) in view of de Vin (IDS Received Date: 05/14/2025; Cite No. 1; Appl. Environ. Microbiol. (2005), 71, 7, 3659-3667; DOI:10.1128/AEM.71.7.3659–3667.2005) as applied to claim 1 and 13, and further in view of Alexandraki (Comparative Genomics of Streptococcus thermophilus Support Important Traits Concerning the Evolution, Biology and Technological Properties of the Species, Front. Microbiol. (2019), 10, 1-24; DOI: 10.3389/fmicb.2019.02916).
Regarding claim 17, An ABSS search alignment shows that SEQ ID NO: 1 aligns 100% to base pairs 1454790-1465831 of S. thermophilus NCTC12958 strain genomic sequences (NCBI Accession Number: LS483339.1; Pub Date: 17 Jun 2018), which encodes for genes in the lac and gal operon including lacZ, lacS, galM, galE, galT, galK, and galR. In addition, Alexandraki discloses NCTC12958 “seem to be able to catabolize galactose, as they own the relevant G to A mutation in the position -9 of the -10-box related Gal1+ phenotype” (pg. 8, right-column, first paragraph), while noting that experimental verification was anticipated.
de Vin confirms that seven S. thermophilus, including EU20 carrying SEQ ID NO:2, naturally has “only one difference in the -10 region of the gal promoter” (pg. 3663, right-column), and teaches that this nucleotide mutation correlates with the increased galactose-consumption rate and ability to consume the glucose and galactose moieties of lactose simultaneously (pg. 3662, right-column, second paragraph). de Vin further teaches that this nucleotide substitution yielded a frameshift affecting the amino acid sequence of GalR after position 58 (pg. 3664, left-column, second paragraph), and EU20 had 11 amino acid differences in GalK and 13 amino acid differences in GalT (Table 5).
The obviousness to modify the S. thermophilus Gal- strain of Vaillancourt via complementation with a functional gal-lac gene cluster comprising a galR-galK intergenic region comprising SEQ ID NO: 2 is discussed above as applied to claims 15 and 16. It would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified Vaillancourt’s S. thermophilus Gal- strain with a gal-lac gene cluster consisting of SEQ ID NO: 1 as taught by Alexandraki because it would have merely amounted to a simple substitution of prior art elements according to known methods to yield predictable results. One would have been motivated to have done so for the advantage of increasing galactose-consumption rate, especially in applications involving dairy products to prevent undesirable accumulation of galactose in milk. One would have had a reasonable expectation of success in doing so because i) Vaillancourt teaches a method of generating recombinant S. thermophilus strain by replacement of native and nonfunctional gal operon with functional operon, selection of Gal+ cells, and measurement of galactose consumption, and ii) Alexandrakis teaches relevant mutation in the -10 box of SEQ ID NO: 1, in view of de Vin’s confirmation that single nucleotide substitution confers galactose utilization.
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Vaillancourt (Appl. Environ. Microbiol. (2004), 70, 8, 4596-4603; DOI: 10.1128/AEM.70.8.4596–4603.2004.) in view of Vaughan (Activation of Silent gal Genes in the lac-gal Regulon of Streptococcus thermophilus; Journal of Bacteriology, 2001, 183(4):1184-1194) and de Vin (IDS Received Date: 05/14/2025; Cite No. 1; Appl. Environ. Microbiol. (2005), 71, 7, 3659-3667; DOI: 10.1128/AEM.71.7.3659–3667.2005) as applied to claim 12, and further in view of Anbukkarasi (Preparation of low galactose yogurt using cultures of Gal+ Streptococcus thermophilus in combination with Lactobacillus delbrueckii ssp. Bulgaricus; J Food Sci Technol, 2014, 51(9): 2183-2189).
Regarding claim 27, the obviousness of modifying Vaillancourt’s S. thermophilus Gal- strain with galR-galK intergenic region comprising instantly claimed SEQ ID NO: 2 as taught by de Vin is discussed above as applied to claim 12. Vaillancourt further teaches “recombinant Gal+ strain grew and produced acid more rapidly than the Gal-strain during growth in milk and under time-temperature conditions” (Abstract). Vaillancourt also teaches that derivation of recombinant “food grade equivalent strains may provide an advantage as starter cultures for manufacture of mozzarella cheese and other fermented dairy foods” (pg. 4602, right-column, last paragraph).
However, Vaillancourt does not teach culturing the recombinant S. thermophilus strain with a bacterial strain from the genus of Lactococcus or Lactobacillus.
Anbukkarasi teaches a culture comprising S. thermophilus Gal+ strains and Gal- Lactobacillus delbrueckii in preparation for low galactose yogurt (pg. 2184, col. 2, para. 3) as S. thermophilus is one of the most important starter culture used for yogurt production in combination with L. delbrueckii (pg. 2183, col. 2, para. 2). Anbukkarasi further teaches the culture comprises S. thermophilus Gal+ strains as opposed to Gal- strains because the metabolic defect of unable to metabolize galactose leads to galactose accumulation in dairy products, including browning of mozzarella cheese, production of carbon dioxide by nonstarter bacteria and growth of spoilage microorganisms (pg. 2183, col. 2, para. 2).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have included a L. delbrueckii strain in the culture of Vaillancourt comprising a S. thermophilus Gal+ strain because it would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. One would have been motivated to have done so for the advantage of their complementary metabolic functions and in preparation for low galactose dairy products as taught by Anbukkarasi. One would have had a reasonable expectation of success in doing so because Anbukkarasi teaches a culture comprising both S. thermophilus Gal+ strain and a L. delbrueckii strain.
Subject Matter Eligibility
Regarding claims 12 and 13, it is noted that the claims require a S. thermophilus strain comprising the sequences as defined in SEQ ID NO:2 or a SEQ ID NO: 2 derivative. The only naturally occurring strain consisting SEQ IS NO:2 is EU20, which is the same DSM32823 strain that is excluded by the claims (see specification pg 2, lines 31-36). Therefore, the current claims are directed to a non-naturally occurring strain comprising SEQ ID NO: 2.
Response to the Arguments
Applicant’s remarks received on May 19, 2026, have been fully considered and Examiner’s response are as follows.
Applicant argues that “Vaillancourt restores galactose metabolism through heterologous complementation of a defective galK coding sequence…the present claims, by contrast, reprogram galactose utilization through the sequence-defined modification of endogenous regulatory architecture while preserving the native gal-lac cluster” (pg. 7, para. 3), and “de Vin does not identify the galR-galK intergenic sequence as sufficient or causative, nor does it suggest that this sequence would function predictably when isolated from the EU20 genomic background, which contains multiple additional sequence differences throughout the gal operon” (pg. 7, para. 8).
Previous rejection of claim 1 under 35 U.S.C. 103 has been withdrawn due amendments that changed the scope of the claim. Instantly amended claim 1 has been rejected as being patentable over Vaillancourt in view of Vaughan and de Vin (cited supra).
Further, Applicant’s arguments have been fully considered but they are not persuasive because Vaughan, cited in instant Office Action, teaches Gal- phenotype arises from inactive wild-type galK promoters lacking “promoter-up mutations” and not enabling transcription of the galK gene, rather than defective galK coding sequences (pg. 1192, col. 1, para. 2; pg. 1189, col. 1, para. 1; pg. 2001, col. 1, para. 1; Fig. 3A). Thus, Vaughan teaches that Gal- phenotype is caused by naturally occurring mutations in the galK promoter (i.e., galR-galK intergenic region), leading to poor expression of the gal operon. Vaughan further validates this finding via sequence analysis of nine other independently isolated S. thermophilus Gal+ strains which every isolate comprises a point mutation in the galK promoter (pg. 1192, col. 1, para. 1). In addition, as stated in previous Office Action mailed on March 20, 2026, Vaillancourt teaches “recombination comprised of the entire galK gene with its own ribosome binding site, as well as the promoter region of the gal operon” (pg. 5, discussion regarding claim 7). Thus, Vaughan restores galactose metabolism through heterologous complementation of galK gene and promoter from S. salivarius. In view of teachings of Vaughan that wild-type galK promoters lacking functional mutations causes Gal- phenotype in S. thermophilus strains, it would have been obvious to have modified Vaillancourt’s method to restore galactose metabolism through complementation of galK-mutated promoter from the same species, S. thermophilus as taught by Vaughan. This modification would have merely amounted to applying a known technique to a known product ready for improvement to yield predictable results (see discussion above as applied to instant claim 1).
Applicant argues that “de Vin does not identify the galR-galK intergenic sequence as sufficient or causative, nor does it suggest that this sequence would function predictably when isolated from the EU20 genomic background, which contains multiple additional sequence differences throughout the gal operon” (pg. 7, para. 8).
This argument has been fully considered but it is not persuasive because Vaughan identifies the galR-galK intergenic region as the causative of gal operon expression via measurement of galK activity in Gal+ strains (pg. 1192, col. 1, para. 2; pg. 1189, col. 1, para. 1; pg. 2001, col. 1, para. 1; Fig. 3A). Vaughan further demonstrates galK-mutated promoter alone, isolated from S. thermophilus genome, is capable of driving expression of downstream reporter gene (pg. 1192, paragraph bridging col. 1 and 2). de Vin further teaches that sequence variation within the galR-galK intergenic region is associated with the Gal+ phenotype, across multiple S. thermophilus strains (Table 1; pg. 3665, col. 2, para. 1). Thus, the prior art teaches predictability in generating S. thermophilus Gal+ strains by modifying the galR-galK intergenic region with functional promoters comprising relevant mutations.
Applicant argues that “de Vin does not suggest that regulatory reprogramming, rather than coding-sequence differences or other genomic context, controls the EU20 phenotype” and “Examiner relies on impermissible hindsight rather than an affirmative teaching in the art” (pg. 8, para. 3).
Applicant’s arguments have been fully considered but they are not persuasive because it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Further, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In addition, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Vaillancourt teaches regulatory reprogramming in S. thermophilus Gal- strain to confer Gal+ phenotype, Vaughan teaches galR-galK intergenic regions comprising mutations enables expression of the gal operaon and results in Gal+ phenotype, and de Vin teaches a galR-galK intergenic region from EU20 that is also a S. thermophilus Gal+ strain. The combination of prior art references renders the instant claims obvious as explained in instant Office Action, and response to arguments above.
Applicant argues that “claim 17 depends on claim 1” (pg. 8, last paragraph), and “Vaillancourt, de Vin and Alexandraki, alone or in combination, not only fail to provide motivation needed to arrive at the subject matter presently claimed, they also do not allow a PHOSITA to predict the effects of the present claims” (pg. 9, para. 4).
Applicant’s arguments have been fully considered but they are not persuasive because claim 17 depends on independent claim 13, which does not require the instantly amended limitation in claim 1. Claim 17, as instantly presented, is drawn to a S. thermophilus strain wherein its gal-lac gene cluster consists of SEQ ID NO: 1 or its derivative. As stated in previous Office Action mailed on March 20, 2026, and in instant Office Action, S. thermophilus strain comprising SEQ ID NO: 1 exhibits Gal+ phenotype ad the -10 box of the gal promoter in the gal operon contains a relevant G to A mutation, and de Vin’s teachings confirm single nucleotide mutation correlated with increased galactose-consumption rate and ability to consume the glucose and galactose moieties of lactose simultaneously. Thus, it would have been obvious to have modified Vaillancourt’s method to engineer a S. thermophilus strain comprising SEQ ID NO: 1 as discussed above as applied to claim 17.
Conclusion
No claims are allowed.
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/QIWEN SU-TOBON/
Examiner
Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
Prosecution Insights