The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to Applicants’ amendments/remarks received June 22, 2026.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 4, 6-7 are canceled. Claims 1-3, 5, 8-12, 14-22 are withdrawn. Claim 13 is under consideration.
Priority: This application is a 371 of PCT/JP2021/037285, filed October 8, 2021, which claims benefit to foreign application JP 2020-172077, filed October 12, 2020. A copy of the foreign priority document has been received in the instant application April 11, 2023, and is not in the English language.
Objections and Rejections
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.
Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Makino et al. (2016 J Dairy Sci 99(2): 915-923; previously cited) in view of Berthold-Pluta et al. (2019 Advancements of Microbiology-POSTĘPY MIKROBIOLOGII 58(2): 191-204; previously cited), van de Guchte et al. (2006 PNAS 103(24): 9274-9279; previously cited), Xu et al. (2015 Food Science and Technology Research 21(2): 263-269), JP ‘555 (JP 2012100555 translation, provided by Google patents, 7 pages), and iPROS (iPROS GMS Yamaden creep meter product information sheets 2015: 8 pages).
Makino et al. disclose that lactic acid bacteria have been widely used in fermented foods for thousands of years (at least p. 915). Makino et al. disclose a method for fermenting milk and yogurt comprising mixing yogurt cultures with cultures containing L. delbrueckii ssp. bulgaricus (OLL1073R-1) (at least p. 915-916). Makino et al. disclose screening 139 L. delbrueckii ssp. bulgaricus strains and identifying OLL1073R-1 as the most robust producer of immunostimulatory EPS (exopolysaccharide) (at least p. 915-917). Makino et al. disclose that yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus (OLL1073R-1) had immunostimulatory effects and that EPS produced from L. delbrueckii ssp. bulgaricus (OLL1073R-1) play an important role in this context (at least p. 915). Makino et al. disclose examining the properties of different prepared yogurts, including OLL1073R-1 yogurt, yogurt A, yogurt B (at least p. 916-921). Makino et al. do not explicitly teach that the identified OLL1073R-1 has a DNA encoding a protein composed of an amino acid sequence set forth in SEQ ID NO: 1 and/or evaluating viscosity of the yogurts with a viscometer (or creepmeter).
Berthold-Pluta et al. disclose that EPS synthesized and produced by lactic acid bacteria has a positive effect on increasing viscosity of fermented milk products (at least p. 191). Berthold-Pluta et al. disclose EPS derived from yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus (OLL1073R-1) exerted immunostimulatory effects and that EPS-containing fermented milk have increased viscosity (at least p. 201).
Van de Guchte et al. disclose the genome of Lactobacillus delbrueckii ssp. bulgaricus (at least p. 9274). Van De Guchte et al. disclose the exopolysaccharide (eps) gene clusters present in Lactobacillus delbrueckii ssp. bulgaricus involved in fermentation (at least p. 9278), including an encoded protein involved in the regulation of capsular polysaccharide synthesis having 96.6% sequence identity to instant SEQ ID NO: 1 (see appendix A).
Xu et al. disclose that some researchers have devoted to investigating fermentation performance in L. bulgaricus and selecting L. bulgaricus having superior features (at least p. 263-264). Xu et al. disclose evaluating four different L. bulgaricus strains and their influence various properties, including viscosity and EPS production (at least p. 264-265). Xu et al. disclose preparing fermented milk with the four L. bulgaricus strains and that the viscosity of the fermented milk samples is measured by a viscometer (proRheo R180 viscometer) with a spindle No. 2 at 64 rpm (at least p. 264). Xu et al. disclose the characteristics of the evaluated L. bulgaricus strains and disclose increased viscosity with increased EPS content (at least p. 265). Xu et al. disclose that it is confirmed that EPS is beneficial to enhance viscosity values of fermented milk (at least p. 265).
JP ‘555 discloses measuring gel-like or viscous properties of a liquid milk dessert (at least p. 1). JP ‘555 discloses filling the milk dessert into a cylindrical container having a diameter of 40 mm and a height of 15 mm and evaluating with a creep meter (Yamaden Rheoner RE-3305), 20 mm diameter cylindrical plunger, speed 10 mm/sec (at least p. 2-3).
iPROS discloses that a creep meter is a universal testing machine capable of quantifying texture and sensory attributes (at least p. 1). iPROS discloses that in addition to rheometer measurements, the creep meter can measure the texture of food, as well as the gel strength, viscosity, and viscoelasticity of various substances (at least p. 1-3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the art references and arrive at a method for evaluating lactic acid bacteria for presence or absence of a fermented milk viscosity improving effect, comprising determining whether the lactic acid bacteria is a L. bulgaricus OLL1073R-1 having a DNA encoding a protein composed of an amino acid sequence set forth in SEQ ID NO: 1 (i.e. an eps gene encoding a protein involved in EPS production), and evaluating the lactic acid bacteria (L. bulgaricus OLL1073R-1) as having a fermented milk viscosity improving effect (instant claim 13). The motivation to do so is given by the prior art. Makino et al. disclose a method for fermenting milk and yogurt comprising screening L. bulgaricus strains and identifying OLL1073R-1 as the most robust producer of EPS by examining the properties of different prepared yogurts by different lactic bacteria, including OLL1073R-1 yogurt, where it is disclosed that EPS-containing fermented milk have increased viscosity (Berthold-Pluta et al.) and the L. bulgaricus genome, therefore including OLL1073R-1, comprises nucleic acid molecules encoding for proteins involved in fermentation and in the regulation of capsular polysaccharide synthesis, including a protein having an amino acid sequence of instant SEQ ID NO: 1 (Van de Guchte et al.). Therefore, one of ordinary skill would have a reasonable expectation of success that in a method for fermenting milk and yogurt, lactic acid bacteria strains can be screened and identified for L. delbrueckii ssp. bulgaricus (OLL1073R-1), where the identified L. bulgaricus OLL1073R-1 comprises nucleic acid molecules encoding a protein (i.e. SEQ ID NO: 1) similar to the polysaccharide synthesis protein disclosed in Van de Guchte et al. and has a fermented milk viscosity improving effect because OLL1073R-1 has been identified as the robust producer of EPS.
Regarding the instant limitations “wherein the fermented milk viscosity improving effect is indicated as significantly longer adhesion time of a fermented milk fermented with the lactic acid bacteria compared to an adhesion time of a fermented milk fermented with L. delbrueckii subsp. Bulgaricus 2038” (instant claim 13) it is noted that since Makino et al. disclose identifying a lactic acid bacteria L. bulgaricus OLL1073R-1 comprising the same structural features recited, where Makino et al. further identify L. bulgaricus OLL1073R-1 as the most robust producer of EPS and that it is known that increased viscosity correlates with increased EPS content (Xu et al.), it would follow that the L. bulgaricus OLL1073R-1 identified in the prior art has the recited fermented milk viscosity improving effect of a significantly longer adhesion time.
Regarding the instant limitations wherein the adhesion time is measured using a creepmeter having the recited parameters (instant claim 13), it would have been obvious for one of ordinary skill to arrive at the recited parameters by routine optimization for measuring viscosity. It is known that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). MPEP 2144.05.
In this instance, the prior art Makino et al. identify L. bulgaricus OLL1073R-1 as the most robust producer of EPS (p. 915), where it is further known that increased viscosity correlates with increased EPS content (Xu et al. p. 265). Xu et al. disclose evaluating fermented milk samples by different lactic acid bacteria strains by a viscometer (p. 264). It is further disclosed that a creep meter is a universal testing machine capable of quantifying texture and sensory attributes (iPROS at least p. 1) and that in addition to rheometer measurements, the creep meter can measure the texture of food, as well as the gel strength, viscosity, and viscoelasticity of various substances (at least p. 1-3). Therefore, it would be obvious to one of ordinary skill that the viscosity of fermented milk samples obtained from lactic acid bacteria (or L. bulgaricus strains) can alternatively be measured by a creep meter, where known parameters for measuring a milk product include filling the milk product into a cylindrical container having a diameter of 40 mm and a height of 15 mm and evaluating with a creep meter (Yamaden Rheoner RE-3305), 20 mm diameter cylindrical plunger, speed 10 mm/sec (JP ‘555 at least p. 2-3). Therefore, it would have been obvious for one of ordinary skill to arrive at the recited parameters for a creep meter by routine optimization, to measure viscosity of a fermented milk product produced by the lactic acid bacteria (L. bulgaricus OLL1073R-1) identified in Makino et al. because a creep meter is a universal testing machine and commonly utilized to measure food textures, including viscosity and viscoelasticity, and the recited parameters are similar to the creep meter parameters disclosed in the prior art for measuring texture of a milk product.
Reply: In view of Applicants’ amendments/remarks, the previous 103 rejection has been withdrawn. However, instant claim 13 remains unpatentable under a new 103 rejection over newly cited art references for the reasons noted above.
Regarding Applicants’ remarks that as shown in appendix A, the amino acid at position 40 of Van de Guchte et al. is asparagine (N) which is same as 2038 strain. In contrast, in SEQ ID NO: 1, position 40 is a tyrosine (Y).
Applicants’ remarks are not persuasive. In this instance, instant claim 13 recites the DNA is alternatively selected from a DNA encoding a protein (a) which is composed of an amino acid sequence set forth in SEQ ID NO: 1. Therefore, a protein or polypeptide comprising any two contiguous amino acids set forth in SEQ ID NO: 1 reasonably meets the recited limitations of “an amino acid sequence set forth in SEQ ID NO: 1.”
The instant specification discloses that the lactic acid bacteria identified as having a viscosity improving effect is L. delbrueckii ssp. bulgaricus (OLL1073R-1) (application publication 0010).
The prior art Makino et al. has already identified L. bulgaricus OLL1073R-1 as the most robust producer of EPS (p. 915), where it is known that increased viscosity correlates with increased EPS content (Xu et al. p. 265) and that gene clusters present in Lactobacillus delbrueckii ssp. bulgaricus involved in fermentation (Van De Guchte et al. at least p. 9278), including an encoded protein involved in the regulation of capsular polysaccharide synthesis having 96.6% sequence identity to instant SEQ ID NO: 1 (see appendix A). Therefore, since Makino et al. disclose identifying a lactic acid bacteria L. bulgaricus OLL1073R-1, one of ordinary skill would have a reasonable expectation that the L. bulgaricus OLL1073R-1 comprises nucleic acid molecules encoding a protein (i.e. SEQ ID NO: 1) similar to the polysaccharide synthesis protein disclosed in Van de Guchte et al. and has a fermented milk viscosity improving effect because OLL1073R-1 has been identified as the robust producer of EPS.
Therefore, the claimed invention identifies the same lactic bacteria already identified in the prior art and having the same viscosity improving effect or increased viscosity compared to other L. bulgaricus strains.
Furthermore, before the effective filing date of the claimed invention, a creep meter is a known and recognized universal testing machine capable of quantifying texture and sensory attributes (iPROS at least p. 1) and that in addition to rheometer measurements, the creep meter can measure the texture of food, as well as the gel strength, viscosity, and viscoelasticity of various substances (at least p. 1-3).
Therefore, it would be obvious to one of ordinary skill that the viscosity of fermented milk samples obtained from lactic acid bacteria (or L. bulgaricus strains) can alternatively be measured by a creep meter, where known parameters for measuring a milk product include filling the milk product into a cylindrical container having a diameter of 40 mm and a height of 15 mm and evaluating with a creep meter (Yamaden Rheoner RE-3305), 20 mm diameter cylindrical plunger, speed 10 mm/sec (JP ‘555 at least p. 2-3). Therefore, it would have been obvious for one of ordinary skill to arrive at the recited parameters for a creep meter by routine optimization, to measure viscosity of a fermented milk product produced by the lactic acid bacteria (L. bulgaricus OLL1073R-1) identified in Makino et al. because a creep meter is a universal testing machine and commonly utilized to measure food textures, including viscosity and viscoelasticity, and the recited parameters are similar to the creep meter parameters disclosed in the prior art for measuring texture of a milk product.
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Marsha Tsay whose telephone number is (571)272-2938. The examiner can normally be reached M-F.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
Appendix A
ID Q1G8E4_LACDA Unreviewed; 257 AA.
AC Q1G8E4;
DT 27-JUN-2006, integrated into UniProtKB/TrEMBL.
DT 27-JUN-2006, sequence version 1.
DT 08-OCT-2025, entry version 91.
DE RecName: Full=Tyrosine-protein kinase CpsD {ECO:0000256|ARBA:ARBA00019200};
DE EC=2.7.10.2 {ECO:0000256|ARBA:ARBA00011903};
GN Name=epsIC {ECO:0000313|EMBL:CAI98747.1};
GN OrderedLocusNames=Ldb2009 {ECO:0000313|EMBL:CAI98747.1};
OS Lactobacillus delbrueckii subsp. bulgaricus (strain ATCC 11842 / DSM 20081
OS / BCRC 10696 / JCM 1002 / NBRC 13953 / NCIMB 11778 / NCTC 12712 / WDCM
OS 00102 / Lb 14).
OC Bacteria; Bacillati; Bacillota; Bacilli; Lactobacillales; Lactobacillaceae;
OC Lactobacillus.
OX NCBI_TaxID=390333 {ECO:0000313|EMBL:CAI98747.1, ECO:0000313|Proteomes:UP000001259};
RN [1] {ECO:0000313|EMBL:CAI98747.1, ECO:0000313|Proteomes:UP000001259}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 11842 / DSM 20081 / BCRC 10696 / JCM 1002 / NBRC 13953 /
RC NCIMB 11778 / NCTC 12712 / WDCM 00102 / Lb 14
RC {ECO:0000313|Proteomes:UP000001259};
RX PubMed=16754859; DOI=10.1073/pnas.0603024103;
RA van de Guchte M., Penaud S., Grimaldi C., Barbe V., Bryson K., Nicolas P.,
RA Robert C., Oztas S., Mangenot S., Couloux A., Loux V., Dervyn R., Bossy R.,
RA Bolotin A., Batto J.-M., Walunas T., Gibrat J.-F., Bessieres P.,
RA Weissenbach J., Ehrlich S.D., Maguin E.;
RT "The complete genome sequence of Lactobacillus bulgaricus reveals extensive
RT and ongoing reductive evolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:9274-9279(2006).
CC -!- FUNCTION: Involved in the regulation of capsular polysaccharide
CC biosynthesis. Autophosphorylation of CpsD attenuates its activity and
CC reduces the level of encapsulation. May be part of a complex that
CC directs the coordinated polymerization and export to the cell surface
CC of the capsular polysaccharide. {ECO:0000256|ARBA:ARBA00024964}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] +
CC ADP + H(+); Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:20101, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:61978, ChEBI:CHEBI:456216; EC=2.7.10.2;
CC Evidence={ECO:0000256|ARBA:ARBA00051245};
CC -!- PATHWAY: Capsule biogenesis; capsule polysaccharide biosynthesis.
CC {ECO:0000256|ARBA:ARBA00005132}.
CC -!- SIMILARITY: Belongs to the CpsD/CapB family.
CC {ECO:0000256|ARBA:ARBA00007316}.
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DR EMBL; CR954253; CAI98747.1; -; Genomic_DNA.
DR RefSeq; WP_011544276.1; NC_008054.1.
DR AlphaFoldDB; Q1G8E4; -.
DR STRING; 390333.Ldb2009; -.
DR KEGG; ldb:Ldb2009; -.
DR PATRIC; fig|390333.7.peg.1760; -.
DR eggNOG; COG0489; Bacteria.
DR HOGENOM; CLU_052027_2_4_9; -.
DR BioCyc; LDEL390333:LDB_RS08745-MONOMER; -.
DR UniPathway; UPA00934; -.
DR Proteomes; UP000001259; Chromosome.
DR GO; GO:0005886; C:plasma membrane; IEA:TreeGrafter.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:UniProtKB-ARBA.
DR GO; GO:0004715; F:non-membrane spanning protein tyrosine kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0045227; P:capsule polysaccharide biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd05387; BY-kinase; 1.
DR FunFam; 3.40.50.300:FF:000527; Tyrosine-protein kinase etk; 1.
DR Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 1.
DR InterPro; IPR025669; AAA_dom.
DR InterPro; IPR050445; Bact_polysacc_biosynth/exp.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005702; Wzc-like_C.
DR NCBIfam; TIGR01007; eps_fam; 1.
DR PANTHER; PTHR32309:SF13; FERRIC ENTEROBACTIN TRANSPORT PROTEIN FEPE; 1.
DR PANTHER; PTHR32309; TYROSINE-PROTEIN KINASE; 1.
DR Pfam; PF13614; AAA_31; 1.
DR SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
PE 3: Inferred from homology;
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840};
KW Capsule biogenesis/degradation {ECO:0000256|ARBA:ARBA00022903};
KW Exopolysaccharide synthesis {ECO:0000256|ARBA:ARBA00023169};
KW Kinase {ECO:0000256|ARBA:ARBA00022777};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741};
KW Reference proteome {ECO:0000313|Proteomes:UP000001259};
KW Transferase {ECO:0000256|ARBA:ARBA00022679};
KW Tyrosine-protein kinase {ECO:0000256|ARBA:ARBA00023137}.
FT DOMAIN 51..198
FT /note="AAA"
FT /evidence="ECO:0000259|Pfam:PF13614"
SQ SEQUENCE 257 AA; 28150 MW; 0820304B5DFA88FC CRC64;
Query Match 96.6%; Score 1233; Length 257;
Best Local Similarity 97.3%;
Matches 250; Conservative 2; Mismatches 3; Indels 2; Gaps 1;
Qy 1 MAFGRKKHLNNDTMKNGVKLITLANPQSVISEQFRNIRTYINFMNVDREVKTIVFTSAMA 60
||||||||||||||||||||||||||||||||||||||| ||||||||||||||||||||
Db 1 MAFGRKKHLNNDTMKNGVKLITLANPQSVISEQFRNIRTNINFMNVDREVKTIVFTSAMA 60
Qy 61 SAGKSTVSANVAITMAQAGKKTILVDADLRRPTMHSTFNVSNSNGLTTLLTSRSMEMDAN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SAGKSTVSANVAITMAQAGKKTILVDADLRRPTMHSTFNVSNSNGLTTLLTSRSMEMDAN 120
Qy 121 SVIRESGVENLSILTAGPIPPNPSELLSSKHMLDLIEDLKQEYDMVVLDLAPILDAGETQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SVIRESGVENLSILTAGPIPPNPSELLSSKHMLDLIEDLKQEYDMVVLDLAPILDAGETQ 180
Qy 181 QLTSSLDGTILVVRQAHSQKSAVKRAVELLKLTKSPILGYVMNDVDADGDD--GYGYGYG 238
|||| |:|||||||||:|||||||||||||||||||||||||||||||||| |||||||
Db 181 QLTSFLNGTILVVRQAYSQKSAVKRAVELLKLTKSPILGYVMNDVDADGDDGYGYGYGYG 240
Qy 239 YGYGEEDEKKGLFGRKK 255
|||||| ||||||||||
Db 241 YGYGEEKEKKGLFGRKK 257
Prosecution Insights