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 .
DETAILED ACTION
Applicant’s response filed on 11/10/2025 is duly acknowledged.
Claims 1-16, as currently amended/presented, are pending in this application.
Priority
This application claims foreign priority from an European application EP 22185858.2 filed on 07/19/2022.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Election/Restrictions
Applicant’s election without traverse of the species “SEQ ID NO: 7” (from claim 7 reciting different species of genes encoding “polysaccharide A biosynthesis pathway”) in the reply filed on 11/10/2025 (see REM, p. 5) is acknowledged.
Claim Terms
It is to be noted that the terms “microorganism” or “microbial anti-inflammatory molecule (MAM)” as recited in instant claim 1 have not been specifically defined by applicants in the instant disclosure of record (see for instance, specification, p. 4, 2nd paragraph; p. 6, section “Microorganism”; p. 2, last paragraph). For this office action, plain meaning of the terms have been used for prior art purposes.
It is also to be noted that no such “microorganism comprising a microbial anti-inflammatory molecule (MAM) gene and one or more gene(s) encoding polysaccharide A biosynthesis pathway” (genetically engineered, or otherwise) has been exemplified and/or disclosed by the applicants in the instant disclosure of record (see specification, conceptual disclosure on p. 10-11, “Example”, in particular).
Claim Objections
Claim 1 is objected to because of the following informalities: claim 1 recites abbreviated limitations “UpaY” and “UpaZ” in line 5. Applicants are advised to recite the full names of the gene(s) at least the first time they appear in a claim set. The abbreviated and italicized form of the gene can be recited in a parenthesis along with the full name, at least the first time it appears in a claim set. It is noted that instant specification also does not provide the full names of aforementioned genes “UpaY” and “UpaZ” (see specification, p. 4, line 3, for instance), which should be amended accordingly to provide the full names of the genes on record. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-16 (as presented) 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 recites the following:
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Claim 1 recites limitations “one or more gene(s) encoding polysaccharide A biosynthesis pathway” (lines 2-3), and also requires the limitations of “wherein one or more gene(s) encoding a metabolic pathway is selected from the group consisting of one or more of the genes encoding UpaY…protein” (lines 4-7), which is ambiguous and confusing because it is unclear if the two sets of limitations (i.e. for “one or more gene(s) encoding polysaccharide A biosynthesis pathway” and “one or more gene(s) encoding a metabolic pathway”) refer to the same “one or more gene(s)” that are recited for “metabolic pathway” are they refer to distinct “one or more genes”. Since the term “metabolic pathway” would normally (to an artisan of ordinary skill in the art) encompass the “biosynthesis pathways” as well as biodegradation or catabolic pathways (i.e. both narrower and broader limitations in the same claim), it is unclear if the later recitations of the genes are just exemplary, or are in fact required by the claimed product. The disclosure of record (see instant specification, p. 3, last full paragraph), and dependent claims 2-16, do not specifically provide clarification regarding the two different sets of limitations for “one or more gene(s)” as currently required in instant claim 1. The recitation as currently presented renders the claimed invention indefinite because the metes and bounds of the claimed product does not seem to be properly defined. 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-16 (as presented) are rejected under 35 U.S.C. 103 as being unpatentable over Langella et al (WO 2017/129515 A1; FOR cited as ref. [N] on PTO 892 form) taken with Quevrain et al (2016; NPL cited as ref. [U] on PTO 892 form), Mazmanian et al (2008; NPL cited as ref. [V] on PTO 892 form) and Coyne et al (2001; NPL cited as ref. [W] on PTO 892 form).
Claim 1 is directed to “A microorganism comprising a microbial anti-inflammatory molecule (MAM) gene and one or more gene(s) encoding polysaccharide A biosynthesis pathway for use in the prevention and/or treatment of Inflammatory Bowel Diseases, wherein one or more gene(s) encoding
Claims 6 and 7 have been reproduced as follows:
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267
695
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See also limitations of dependent claims 2-5 and 8-16, as currently presented.
Applicant’s elected species from instant claim 7 is SEQ ID NO: 7.
Langella et al (2017) disclose a Faecalibacterium prausnitzi strain (deposited as accession number CNCM I-4573) intended for the treatment and prevention of Gastrointestinal (GI) tract inflammation and related disorders such as inflammatory bowel disease in an individual in need thereof (see title, Abstract, “Summary of the invention”), wherein said bacterial strain (isolated from healthy male patient; see p. 9, line 5) was unexpectedly demonstrated to reduce GI inflammation, both in vitro as well as in vivo conditions tested, by decreasing pro-inflammatory cytokines and increasing the production of anti-inflammatory cytokine molecules such as interleukin-10 (IL-10; see p. 2, lines 11-21, for instance); wherein said strain is a probiotic strain (see p. 2, lines 28-29), and compositions comprising said strain (regarding instant claims 1, 8-16) can be prepared as pharmaceutical or nutraceutical products for oral administration in suitable medium/carriers, and used for treatment of inflammatory bowel disease (IBD), including Crohn’s disease and ulcerative colitis in patients in need thereof (see p. 3, lines 1-5), for instance in the form of food or beverage compositions including fermented dairy products such as yogurt (see p. 3, lines 6-18; p. 6-7, section “Compositions”; and Claims on p. 18-19, for instance), powdered, or solid dosage forms including various pharmaceutical dosage forms such as tablets, capsules, granules, etc.
Langella et al. does not disclose a microorganism comprising a gene expressing a “microbial anti-inflammatory molecule (MAM)” in combination with one or more genes encoding “polysaccharide A” biosynthetic pathway as recited in instant claim 1 (and genetically engineered bacteria as in instant claims 2-4).
Quevrain et al (2016), while teaching the identification and characterization of an anti-inflammatory protein of 15 KDa isolated from commensal bacterium, Faecalibacterium prausnitzii (see Title, Abstract, p. 15 “Summary Box”, and Table 1 on p. 26, disclosed as “Protein ZP 05614546.1”) designated as “Microbial Anti-inflammatory Molecule (MAM)”, disclose genetically modified bacteria comprising gene encoding said MAM (which was PCR amplified from genomic DNA of F. prausnitzii), including Escherichia coli as expression host (see p. 4, section “Production of MAM protein in a bacterial heterologous system”), and Lactococcus lactis as a delivery vector for in vivo experiments (see p.5, section “In vivo assays for anti-inflammatory effect of MAM protein”; p. 24, Fig. 9); wherein the MAM protein ZP 05614546.1, is 100% identical to applicant’s disclosure for 15 KDa MAM protein of amino acid sequence of SEQ ID NO: 2 (that is derived from the nucleic acid sequence SEQ ID NO: 1 in instant claim 6; see instant Specification, p. 3, lines 26-29; and p. 6, section “Genes”, in particular) derived from the same commensal bacteria species F. prausnitzii as shown below (Qy is SEQ ID NO: 2 of the instant application; Db is MAM Protein ZP 05614546.1 disclosed by Quevrain et al, p. 26, Table 1):
AMINO ACID SEQUENCE ALIGNMENT:
RESULT 1
AASEQ2_01232026_082104
Query Match 100.0%; Score 699; DB 1; Length 135;
Best Local Similarity 100.0%;
Matches 135; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MMMPANYSVIAENEMTYVNGGANFIDAIGAVTAPIWTLDNVKTFNTNIVTLVGNTFLQST 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MMMPANYSVIAENEMTYVNGGANFIDAIGAVTAPIWTLDNVKTFNTNIVTLVGNTFLQST 60
Qy 61 INRTIGVLFSGNTTWKEVGNIGKNLFGTNVKGNPIEKNNFGDYAMNALGIAAAVYNLGVA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 INRTIGVLFSGNTTWKEVGNIGKNLFGTNVKGNPIEKNNFGDYAMNALGIAAAVYNLGVA 120
Qy 121 PTKNTVKETEVKFTV 135
|||||||||||||||
Db 121 PTKNTVKETEVKFTV 135
Quevrain et al disclose the fact that “F. prausnitzii is a major inducer of Clostridium-specific IL-10-secreting regulatory T cell subset present in the human colonic lamina propria and blood” (see p. 11, 1st paragraph; and cited references therein), which was one of the art-known anti-inflammatory cytokines (among other factors) helping to restore, maintain and shape gut barrier immune function. Thus, genetically engineered bacteria (E. coli as well as L. lactis) comprising a “microbial anti-inflammatory molecule (MAM) gene” have been nevertheless fully disclosed by Quevrain et al.
Quevrain et al. do not disclose genetically engineered bacteria that also comprise (i.e. in addition to MAM protein gene from F. prausnitzii) one or more biosynthesis genes for “polysaccharide A” (regarding instant claim 1), they do disclose the art-known fact that “[O]ther species-specific bacterial molecules, such as B. fragilis-derived polysaccharide A, have previously been demonstrated to have immunomodulatory functions…” (see p. 11, 1st paragraph; and cited references therein), eluding to complex interplay involving different species of gut commensal bacteria and their various metabolic products that help limit the inflammatory processes in the GI tract.
Mazmanian et al (2008) disclose the microbial symbiosis factor “polysaccharide A” (PSA; see Title, Abstract on p. 620) that acts as a gut immunomodulatory molecule and prevents intestinal inflammatory disease; wherein they disclose that “…the prominent human symbiont Bacteroides fragilis strain 9343 protects animals from experimental colitis induced by Helicobacter hepaticus, a commensal bacterium with pathogenic potential. This beneficial activity requires a single microbial molecule (polysaccharide A, PSA)…. Furthermore, PSA protects from inflammatory disease through a functional requirement for interleukin-10-producing CD41 T cells” (see Abstract on p. 620); wherein “animals harbouring B. fragilis not expressing PSA, H. hepaticus colonization leads to disease and pro-inflammatory cytokine production in colonic tissues”, directly demonstrating the beneficial effects of a commensal bacteria producing PSA for gut inflammatory disorders including IBD (see p. 620, right column, 2nd paragraph; and p. 621, section “Protection from colitis by B. fragilis”, for instance); wherein they experimentally demonstrated that IL-10 is required for PSA-mediated protection from intestinal inflammation and experimental colitis (see p. 624, Figure 5, for instance). Thus, Mazmanian et al disclose the fact that B. fragilis naturally expresses an anti-inflammatory PSA molecule, and B. fragilis strain that does not express PSA (such as DPSA), does not show the beneficial effects in the gut of animals having inflammatory disease.
Although Mazmanian et al. do not explicitly disclose the genes encoding “polysaccharide A” biosynthesis pathway, such would have been obvious to an artisan of ordinary skill in the art because Coyne et al (2001) had already disclosed the locus of the chromosomal genes from B. fragilis strain 9343 for polysaccharide biosynthesis (see Coyne et al, Title, Abstract on p. 4342; Table 1 on p. 4343, section “Creation of deletion mutant 9343DPSA”; Figure 1; and p. 4345, entire section “Genetic complement of the PS A locus”, for instance) that comprises such biosynthesis genes including gene encoding PSA (that is common to all species of B. fragilis, and that has been disclosed as expressing a “putative flippase” with Protein ID of “AAK68914.1”, and has 100% identity to nucleic acid sequence of SEQ ID NO: 7, applicant’s elected species for a gene from instant claim 7; see below for the nucleic acid sequence homology search results), and the fact that they had provided all the information for construction and genetic manipulations for making DPSA chromosomal mutant employed in the cited reference of Mazmanian et al, as discussed above (see Mazmanian et al, P. 623, section “IL-10-producing T cells suppress colitis”; and p. 624, section “Methods Summary”, for instance). The sequence homology for SEQ ID NO: 7 is as follows:
SEQ ID NO: 7 (Query: Instant claim 7):
RESULT 1 (GenEmbl database)
AF189282
LOCUS AF189282 16792 bp DNA linear BCT 23-JUL-2016
DEFINITION Bacteroides fragilis NCTC 9343 capsular polysaccharide A gene
locus, partial sequence.
ACCESSION AF189282
VERSION AF189282.1
KEYWORDS .
SOURCE Bacteroides fragilis NCTC 9343
ORGANISM Bacteroides fragilis NCTC 9343
Bacteria; Bacteroidota; Bacteroidia; Bacteroidales; Bacteroidaceae;
Bacteroides.
REFERENCE 1 (bases 1 to 16792)
AUTHORS Coyne,M.J., Tzianabos,A.O., Mallory,B.C., Carey,V.J., Kasper,D.L.
and Comstock,L.E.
TITLE Polysaccharide biosynthesis locus required for virulence of
Bacteroides fragilis
JOURNAL Infect. Immun. 69 (7), 4342-4350 (2001)
PUBMED 11401972
REFERENCE 2 (bases 1 to 16792)
AUTHORS Coyne,M.J. Jr. and Comstock,L.E.
TITLE Direct Submission
JOURNAL Submitted (23-SEP-1999) Channing Laboratory, Brigham & Women's
Hospital/Harvard Medical School, 181 Longwood Avenue, Boston, MA
02115-5821, USA
FEATURES Location/Qualifiers
source 1..16792
/organism="Bacteroides fragilis NCTC 9343"
/mol_type="genomic DNA"
/strain="NCTC 9343"
/type_material="type strain of Bacteroides fragilis"
/db_xref="taxon:272559"
/note="polysaccharide genes named in accordance with the
Bacterial Polysaccharide Gene Nomenclature scheme
(Reeves,P.R., et al. Trends Microbiol. 1996,
4(12):495-503.)"
CDS 98..1102
/note="ORF1"
/codon_start=1
/transl_table=11
/product="unknown"
/protein_id="AAK68911.1"
/translation="MNLKFLYLLLLISALCISCSKDEEPSDKGSTSPQEPVYTTFTDA
GEVVVPGVLPANFTPRSVRVKGDTLFVANTNAADRSVLLLNLTTGELIGRIDSWVRKG
VKETFNAEIGDMAVSDRYIFVGMYNSRINIFDRRTLQFVNAIGRSDGKWGDDIYSMTH
CYGLRECGERLMVRDKNTIRGYWIYEAVTEPAFRVPWIGKVKVPEGVGYDYQARIHGM
AEYDGRMYLTDWYNKSVQVFTPSKMEIVFGEETHITSDAVFKYDDIQPLGLLAYGGEL
LMSVQKSGKIQRYDPETGDLLGVLAEFPGKEIGRMEIARGMLYYIDLKAGKLMKAKGE
"
gene 2425..2943
/gene="upaY"
CDS 2425..2943
/gene="upaY"
/codon_start=1
/transl_table=11
/product="UpaY"
/protein_id="AAK68912.1"
/translation="MSEQQEYWFAARTKKDQEFSVRNALEKLGIEYFLPTQFVIRQLK
YRRRRVEVPVIKNLIFVRTTKDRAWSITKDDHVPLYYMKDLYTHTLLIVPNKQMEDFK
FVMDLAPENVTFDDLPLTVGTKVQVVKGEFCGIEGELSSLANRTYVVIRIHGVLSASV
KVPKSYLRILSA"
gene 2963..3436
/gene="upaZ"
CDS 2963..3436
/gene="upaZ"
/codon_start=1
/transl_table=11
/product="UpaZ"
/protein_id="AAK68913.1"
/translation="MNQVQNLQHIARELLYLGMDGSPIYTDHFRQLNTEVFRLSEALF
SMKGATSEEEAAICLSLLMGYNATIYNDGDKESKIQSILDRSFAVLDHLPASLLKCQL
LTYCYGEVFEEDLAQEAHQIMDSWKNRALSEEELEVMETLQTMEDNRYPCSEVED"
gene 3504..4952
/gene="wzx"
CDS 3504..4952
/gene="wzx"
/codon_start=1
/transl_table=11
/product="putative flippase"
/protein_id="AAK68914.1"
/translation="MGQSIKNNFLLNLSTTITGLLFPLITFPYASRILMADGIGQVQF
FQSIIDYVSLCTALGIPLYAVREIARIRDNKELRSRTTIEILLLHAILTLVGYIVVFI
LAKTVAKIEIDASLFFLLSTTLFFNTIGVAWFYQAIEDFKYITLRSLFVRILSLVALF
IFVKTKQDLFYYAGILVIGTVGNNIFNFFRLRKYIKLSKGEFKRLNLLRHLIPALKIF
ILNLVISIYVNLDSVMLGFLKNEESVGYYAAATRLTKAILGIVSSLGAVLLPRFSNMI
TNGQKEEFQLLANKAASFTIALSLPMSVGLIFMAAPIIHIFCGNGFEPSILTLKLVAP
IVLFIGLSGIIGMQILYPQGREKYVIISTMVGACINLLINYLLIPQYGQYGAALGTVI
AEFMVTVIMILLGRKYLPINILSKQNLHYLIGSIVISILLAFLFVFPLHEVNYLLIGI
LLSVIVYYAYLLMIKDTLALQLKKLLLSIFKQ"
gene 4949..6043
/gene="wcfM"
CDS 4949..6043
/gene="wcfM"
/codon_start=1
/transl_table=11
/product="putative galactopyranose mutase"
/protein_id="AAK68915.1"
/translation="MKKKYDYLIVGAGLYGSVFAYKAQRNGKKCLLIDKRPHNGGNIY
CENIEGINVHKYGAHIFHTSNKEVWDFVNAIVEFNRYTNSPIANYKGKLYNLPFNMNT
FYALWGTKTPEEAKMKIEEQRREAGILTPKNLEEQAISLVGKDIYEILIKGYTEKQWG
RKATELPAFIIKRLPVRFTFDNNYFNDKYQGIPVGGYNKLINGLLDGIEVRTNTDFFQ
NKEYFKGLADKILFTGKIDEYYNYQFGRLEYRTVEFETQVLDCENYQGNAVVNYTERE
VPYTRIIEHKHFEFGTQPKTVISKEYSSEWKDGSEPFYPVNDERNNSLYLEYKKLVDR
EKNVLFGGRLAEYKYYDMNVIVEKVINSDL"
gene 6040..6915
/gene="wcfN"
CDS 6040..6915
/gene="wcfN"
/codon_start=1
/transl_table=11
/product="putative glycosyltransferase"
/protein_id="AAK68916.1"
/translation="MKIFAVVVTYNRLALLKKVIDLLKRQTRQLDSIVIVNNGSTDGT
KEWLEQEKNITLINQSNSGGAGGFETGVKYAYENEADWIWMMDDDVFPNIDCLEKLLG
WTSISQCIQPRRYYSDDVEVNFEQWLDPITYSKFGYWQEKSFNNGKKFCAINVGCFEG
MFVSKSIVNKIGFPDKRFFIAEDDTIYGFAASFYTNVILVSDAIMVRARRSSDRSVSP
MYTYYACRNFHLVYESLNLLLDKKNRFLYIKYIYQFVHQIYLSIFLYDNKMKHLISVF
RGFYDCFRKKNGATY"
gene 6920..8224
/gene="wzy"
CDS 6920..8224
/gene="wzy"
/codon_start=1
/transl_table=11
/product="putative polymerase"
/protein_id="AAK68917.1"
/translation="MTSTSFFIIKAISFIVFVYNLASSDWSNLSRVLLFIISFFVFLL
VTNVYQRKVKIVTLGYLVYFFLAFLAQNVGPYAIIYNSHIQNLIQRFPNICVPNDHYT
LYFLIFIFVSTVIYIYLLCIDKISIEQKVWVYMPTRQEARKIMMAFFIILLPIWILGN
RSYATILVPFTSYFIISIWKYPFTRKIVVFIIGFIASVLILISQLFSRFIFVQYVFPF
ILIWFLNNGLLFSRKEKISYKVIGFFLLFCSLAILYGIISEMMKLNANFDGNYTFNDM
FEVLSEPQLLQNWLSRQTYRIFDIWSHLGGNIIDYIDQKGYLWGITYVKSFAPILGFD
YVSLPLISANMIGADYAQPGLVAEGYANWGIYGAIINMIFVFFVAELLFDYFLRKQST
LNLLLYIGTFSQVLLDGGTINSIIFMSIFCFLTCLFNAKIKF"
gene 8235..9278
/gene="wcfO"
CDS 8235..9278
/gene="wcfO"
/codon_start=1
/transl_table=11
/product="putative glycosyltransferase"
/protein_id="AAK68918.1"
/translation="MRKILLTYGDIKTINIGDYIQSIAAKQFFDDDNYIFFNRDELKL
YKGEPAKVIMNAWMTYKPYNWPPSSQVYPLFVALHINSSAESRFLSHDSIKYLKKYEP
IGCRDYHTMNILKGKGVNAYFSGCLTTTLGKTYKYNGKREGIYIVDPLSYMPNGNNFF
EIMKAVVQTVFYMKPVLKILRNYKKNNRFTINISKVGIGRLLLITKSYLLLRKLVVPD
VLYNAIFITQFNMSNEYSSESERFARADELLTKMASAQYVITSRIHCALPCLGFETPV
VYIRNLSESKKSTCRLGGLESLFNVITVKGENVTSNFFDGLFKRDSSFKNKIDFVEYR
DRLINICNKFMMS"
gene 9275..10411
/gene="wcfP"
CDS 9275..10411
/gene="wcfP"
/codon_start=1
/transl_table=11
/product="putative glycosyltransferase"
/protein_id="AAK68919.1"
/translation="MRDGKPIEILHIVGTRPVGGIGALLKNINTSIDLNKFHFTYVFS
ADSNIGDFDNYVRKLGSDIVVFPSYHLKYLFLYLKVIFCFYKRNAKKYDIIHVHSANT
GVLDLLFAKIYGIRIRILHSHSTKYSSKKIRSIRNYFLQFPTIYLANTYFACGYKAAE
FLFGKKRLEKVYIIHNAIFSKKFIYNATVRERVRVELKIENDCLLLGHIGNFTKEKNH
GFLIDILEELLNINDNVKLLLVGDGQLRSEIEEKVKLKRLQKYVCFLGRRTDISELLQ
AMDFLIFPSFFEGLPVTLIEAQASGLRCVVSDRITLETKITNNISYLNLNRDPSTWAE
VVWKLFEDKTFIRKDTSKEICESGYDIHLESEYLERIYLNLLHK"
gene 10408..11214
/gene="wcfQ"
CDS 10408..11214
/gene="wcfQ"
/codon_start=1
/transl_table=11
/product="putative glycosyltransferase"
/protein_id="AAK68920.1"
/translation="MKLAVISSIYKNDSLSKIKQSLQSLLNQENVTCDIYLYCDGPVS
IDIVHFLDSFDQNSLYIFKQEQNRGLAHALNELLNIVLTKEYEYIARMDADDISMPER
FVKQIAFMNSHPDIDCLGTWAIEIDDDGKEYFRKKMPITHEECLELFKKRDCMIHPTV
MFRRSYFEKAGLYPEDTYFGEDTMMWAKGFKSGCKFANVPEYLFKFRLDSNFFERRRG
WKHAKSIYTLRHRVNRMLGFGWKEDCYALLYAMAKLMPKSILDIIYKTVR"
gene 11243..12466
/gene="wcfR"
CDS 11243..12466
/gene="wcfR"
/codon_start=1
/transl_table=11
/product="putative amino sugar synthetase"
/protein_id="AAK68921.1"
/translation="MKIPFSPPYIDEAVINEVVDSLRSGWITSGPKVKALEEEIKSFS
GAKEVLCVNSWTSGAIMMLRWLGVKEGDEVIVPAYTYSATALAVLHAGAKPVMVDSGT
DFNISVEAVRKAITPKTKAIIPVDIAGFPCDYERIMALVQEPEMVKLFRSESPVQEKL
GRILVMNDAAHSLGARYSSRQRTGCETDVAIFSLHAVKNVTTAEGGAICLNLPKPFDN
TELYKELRMTSLNCQTKDAFSKSKAGGWRYDIVGFGMKINMADVNAAIGLAQIREYPE
LLKERKRVFNAYSDAFSACDWAIVPPSVDGEKESSYHIYALRIKDFTEEQRDRMIDEI
AKSEVAVNVHFIPMPMLSFFKSMGYDIKDYPQAYQNFKSEISLPIYPQLDSEKLNFII
ETVKAAYATVIAENR"
gene 12489..13085
/gene="wcfS"
CDS 12489..13085
/gene="wcfS"
/note="may utilize an alternative start codon"
/codon_start=1
/transl_table=11
/product="putative undecaprenyl-phosphate galactose
phosphotransferase"
Query Match 100.0%; Score 1449; Length 16792;
Best Local Similarity 100.0%;
Matches 1449; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGGGACAATCAATAAAGAATAACTTCCTACTGAATCTAAGTACTACAATTACTGGGCTA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3504 ATGGGACAATCAATAAAGAATAACTTCCTACTGAATCTAAGTACTACAATTACTGGGCTA 3563
Qy 61 TTATTTCCACTAATAACTTTTCCCTATGCTTCACGTATATTAATGGCAGATGGTATAGGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3564 TTATTTCCACTAATAACTTTTCCCTATGCTTCACGTATATTAATGGCAGATGGTATAGGG 3623
Qy 121 CAAGTACAATTTTTCCAATCCATAATTGACTATGTCTCTCTTTGTACTGCTTTGGGAATC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3624 CAAGTACAATTTTTCCAATCCATAATTGACTATGTCTCTCTTTGTACTGCTTTGGGAATC 3683
Qy 181 CCTTTGTATGCCGTTAGAGAAATTGCAAGAATAAGGGATAATAAGGAATTAAGAAGTAGA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3684 CCTTTGTATGCCGTTAGAGAAATTGCAAGAATAAGGGATAATAAGGAATTAAGAAGTAGA 3743
Qy 241 ACAACAATCGAAATACTATTGCTTCATGCTATTTTGACTTTAGTCGGATATATAGTTGTT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3744 ACAACAATCGAAATACTATTGCTTCATGCTATTTTGACTTTAGTCGGATATATAGTTGTT 3803
Qy 301 TTTATACTTGCTAAGACCGTTGCCAAAATAGAAATAGATGCTTCTCTTTTCTTTTTGTTA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3804 TTTATACTTGCTAAGACCGTTGCCAAAATAGAAATAGATGCTTCTCTTTTCTTTTTGTTA 3863
Qy 361 AGTACAACTTTATTTTTTAACACGATAGGAGTTGCATGGTTTTATCAGGCAATTGAAGAT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3864 AGTACAACTTTATTTTTTAACACGATAGGAGTTGCATGGTTTTATCAGGCAATTGAAGAT 3923
Qy 421 TTTAAATACATAACTTTACGTTCCTTATTTGTAAGGATACTATCTTTAGTGGCCTTATTT 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3924 TTTAAATACATAACTTTACGTTCCTTATTTGTAAGGATACTATCTTTAGTGGCCTTATTT 3983
Qy 481 ATCTTTGTTAAGACCAAGCAAGATCTGTTTTATTATGCTGGAATATTAGTTATTGGTACT 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 3984 ATCTTTGTTAAGACCAAGCAAGATCTGTTTTATTATGCTGGAATATTAGTTATTGGTACT 4043
Qy 541 GTTGGTAATAATATATTTAATTTTTTTCGATTACGTAAATATATAAAACTTAGTAAAGGC 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4044 GTTGGTAATAATATATTTAATTTTTTTCGATTACGTAAATATATAAAACTTAGTAAAGGC 4103
Qy 601 GAATTTAAGCGTTTGAATCTGTTGAGGCATTTAATACCTGCACTTAAAATTTTTATATTA 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4104 GAATTTAAGCGTTTGAATCTGTTGAGGCATTTAATACCTGCACTTAAAATTTTTATATTA 4163
Qy 661 AATTTGGTTATAAGTATTTATGTGAATCTTGATTCTGTGATGCTTGGATTTCTTAAAAAT 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4164 AATTTGGTTATAAGTATTTATGTGAATCTTGATTCTGTGATGCTTGGATTTCTTAAAAAT 4223
Qy 721 GAAGAATCAGTTGGTTATTATGCTGCTGCTACTCGACTTACAAAAGCTATTTTGGGTATA 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4224 GAAGAATCAGTTGGTTATTATGCTGCTGCTACTCGACTTACAAAAGCTATTTTGGGTATA 4283
Qy 781 GTTTCTTCATTAGGAGCTGTTTTATTACCTCGTTTTAGTAATATGATAACTAATGGTCAA 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4284 GTTTCTTCATTAGGAGCTGTTTTATTACCTCGTTTTAGTAATATGATAACTAATGGTCAA 4343
Qy 841 AAAGAAGAATTCCAATTATTGGCAAATAAAGCTGCTAGTTTTACAATTGCTTTAAGTCTT 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4344 AAAGAAGAATTCCAATTATTGGCAAATAAAGCTGCTAGTTTTACAATTGCTTTAAGTCTT 4403
Qy 901 CCTATGAGTGTGGGACTTATTTTTATGGCAGCACCTATTATACATATTTTTTGTGGAAAT 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4404 CCTATGAGTGTGGGACTTATTTTTATGGCAGCACCTATTATACATATTTTTTGTGGAAAT 4463
Qy 961 GGTTTTGAACCTTCTATTTTGACATTAAAATTAGTTGCACCTATTGTTTTATTTATTGGA 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4464 GGTTTTGAACCTTCTATTTTGACATTAAAATTAGTTGCACCTATTGTTTTATTTATTGGA 4523
Qy 1021 TTATCTGGAATTATTGGAATGCAAATATTGTATCCGCAAGGGAGAGAAAAGTACGTAATT 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4524 TTATCTGGAATTATTGGAATGCAAATATTGTATCCGCAAGGGAGAGAAAAGTACGTAATT 4583
Qy 1081 ATATCTACTATGGTAGGAGCATGTATAAATCTCCTTATAAACTATTTACTAATACCCCAA 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4584 ATATCTACTATGGTAGGAGCATGTATAAATCTCCTTATAAACTATTTACTAATACCCCAA 4643
Qy 1141 TATGGGCAGTATGGAGCGGCGCTTGGGACTGTTATCGCAGAATTTATGGTAACGGTTATA 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4644 TATGGGCAGTATGGAGCGGCGCTTGGGACTGTTATCGCAGAATTTATGGTAACGGTTATA 4703
Qy 1201 ATGATTTTGCTGGGAAGAAAATATTTACCTATAAATATTCTCTCCAAGCAGAATTTACAC 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4704 ATGATTTTGCTGGGAAGAAAATATTTACCTATAAATATTCTCTCCAAGCAGAATTTACAC 4763
Qy 1261 TATCTAATAGGTTCTATAGTGATATCTATTCTATTAGCTTTTTTGTTTGTCTTCCCTTTA 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4764 TATCTAATAGGTTCTATAGTGATATCTATTCTATTAGCTTTTTTGTTTGTCTTCCCTTTA 4823
Qy 1321 CATGAAGTAAATTATTTATTGATAGGTATACTGTTATCTGTTATTGTTTATTACGCATAT 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4824 CATGAAGTAAATTATTTATTGATAGGTATACTGTTATCTGTTATTGTTTATTACGCATAT 4883
Qy 1381 TTATTAATGATAAAAGATACCCTCGCATTACAACTAAAGAAATTATTACTTTCAATATTT 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 4884 TTATTAATGATAAAAGATACCCTCGCATTACAACTAAAGAAATTATTACTTTCAATATTT 4943
Qy 1441 AAACAATGA 1449
|||||||||
Db 4944 AAACAATGA 4952
Although the focus of Coyne et al was for identifying the role of polysaccharide biosynthesis locus genes including PSA in relation to virulence of B. fragilis 9343 strain, they nevertheless disclose all the required details for an artisan in order to perform required genetic manipulations to identify, amplify, clone/transfer, and/or mutate such polysaccharide biosynthesis loci or genes in a desired bacteria.
Thus, given the detailed disclosure for the roles of two different gut commensal bacteria-based anti-inflammatory molecules (MAM and polysaccharide A), as taught in the cited prior art references of Quevrain et al when taken with the disclosure from Mazmanian et al and Coyne et al, it would have been obvious to an artisan of ordinary skill in the art to modify the composition disclosed by Langella et al comprising commensal bacteria Faecalibacterium prausnitzii that are known to possess gene and express 15 KDa anti-inflammatory MAM protein (as explicitly taught by Quevrain et al) in combination with one or more polysaccharide A biosynthesis gene(s) such as a flippase (as specifically taught by Mazmanian et al when taken with Coyne et al, as discussed above) in order to enhance the efficacy of the compositions comprising commensal bacteria Faecalibacterium prausnitzii that can be employed for treatment and/or prevention of gut inflammation and related disorders including IBD, ulcerative colitis, et c., as already eluded and/or suggested by all the three cited prior art references of Langella et al taken with Quevrain et al and Mazmanian et al discussed above. Since, such genetic manipulation techniques for chromosomal as well as plasmid amplification/cloning, etc. were already known in the prior art as provided by the cited prior art of Coyne et al as discussed above, an artisan in the art would have had a reasonable expectation of success in modifying the desired commensal bacteria in order to create a genetically engineered variant that comprises a combination of both genes (i.e. encoding for MAM protein as well as polysaccharide A) that are disclosed in the prior art for their IL-10-based anti-inflammatory response in the gut of human individuals, or in patients having gut inflammation and/or related disorders such as IBD, Crohn’s disease, ulcerative colitis, etc. Since, Langella et al already disclose suitable compositions (such as food, beverage, pharmaceutical solid dosage forms, etc.; see detailed teachings above) comprising efficacious commensal probiotic bacteria F. prausnitzii strain that is used for increasing production of anti-inflammatory molecules of IL-10 in the gut, such modification of the strain providing combination of two different anti-inflammatory molecules would be expected to enhance the efficacy of treatment and/or prevention of gut inflammatory disorders in patients in need thereof, as already eluded and/or desired by the cited prior art of Langella et al.
It is to be noted that instant claims are directed to a “microorganism” (instant claim 1) reciting specifically “bacteria, yeast or fungi” (see instant claims 2-4) produced by genetic engineering. However, the disclosure of record appears to be mainly conceptual, and fails to provide any such example(s) of the genetically engineered bacteria, yeast or fungi per se (see instant specification, p. 10-11, “Example”, for instance). Applicants are reminded that the scope of the showing must be commensurate with the scope of claims to consider evidence probative of unexpected results, for example. In re Dill, 202 USPQ 805 (CCPA, 1979), In re Lindner 173 USPQ 356 (CCPA 1972), In re Hyson, 172 USPQ 399 (CCPA 1972), In re Boesch, 205 USPQ 215, (CCPA 1980), In re Grasselli, 218 USPQ 769 (Fed. Cir. 1983), In re Clemens, 206 USPQ 289 (CCPA 1980). It should be clear that the probative value of the data provided on record (see instant claim 1, in particular) is not commensurate in scope with the degree of protection sought by the claim.
Thus, the claim as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the invention as claimed.
As per MPEP 2111.01, during examination, the claims must be interpreted as broadly as their terms reasonably allow. In re American Academy of Science Tech Center, F.3d, 2004 WL 1067528 (Fed. Cir. May 13, 2004)(The USPTO uses a different standard for construing claims than that used by district courts; during examination the USPTO must give claims their broadest reasonable interpretation.). This means that the words of the claim must be given their plain meaning unless applicant has provided a clear definition in the specification. In re Zletz, 893 F.2d 319, 321, 13 USPQ2d 1320, 1322 (Fed. Cir. 1989).
SEQUENCE ALIGNMENTS
SEQ ID NO: 1 (Query: Instant claim 6):
RESULT 1 (Geneseq database)
BBJ30778
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BBJ30778 standard; DNA; 408 BP.
XX
AC BBJ30778;
XX
DT 28-AUG-2014 (first entry)
XX
DE F. prausnitzii protein (ZP05614546.1) encoding DNA, SEQ ID: 19.
XX
KW allergic rhinitis; allergy; alzheimers disease; anaphylaxis;
KW antiinflammatory; arthritis; atopic dermatitis; autoimmune disease;
KW contact dermatitis; crohns disease; diabetes mellitus; ds; eczema;
KW encephalitis; enteritis; gene; glomerulonephritis;
KW graft versus host disease; hypersensitivity; ileitis; immunosuppressive;
KW inflammatory bowel disease; inflammatory disease; meningitis;
KW multiple sclerosis; neuroprotective; nootropic; osteoarthritis;
KW prophylactic to disease; protein therapy; systemic lupus erythematosus;
KW therapeutic; transplant rejection; ulcerative colitis; urticaria;
KW vasculitis.
XX
OS Faecalibacterium prausnitzii.
XX
FH Key Location/Qualifiers
FT CDS 1..408
FT /*tag= a
FT /product= "Faecalibacterium prausnitzii derived protein
FT (ZP05614546.1)"
XX
CC PN WO2014102009-A1.
XX
CC PD 03-JUL-2014.
XX
CC PF 26-DEC-2013; 2013WO-EP003917.
XX
PR 26-DEC-2012; 2012EP-00008611.
XX
CC PA (INRG ) INRA INST NAT RECH AGRONOMIQUE.
XX
CC PI Langella Philippe;
XX
DR WPI; 2014-M43615/46.
DR P-PSDB; BBJ30761.
XX
CC PT New polypeptide useful for treating or preventing inflammatory diseases
CC PT e.g. inflammatory bowel disease, e.g. enteritis, comprising or consisting
CC PT of specified amino acid sequence, and conservative derivative or its
CC PT fragment.
XX
CC PS Claim 8; SEQ ID NO 19; 55pp; English.
XX
CC The present invention relates to a novel polypeptide useful for treating
CC or preventing inflammatory diseases. The invention further includes: a
CC nucleic acid sequence encoding the polypeptide; a vector comprising the
CC nucleic acid sequence; a host cell which has been transfected, infected
CC or transformed by the nucleic acid sequence; and a pharmaceutical
CC composition comprising the polypeptide, the nucleic acid sequence, the
CC vector or host cell and carrier. The polypeptide is also useful for
CC preventing: inflammatory diseases chosen from inflammatory bowel disease,
CC ulcerative colitis, ileitis and enteritis, Crohn disease, systemic
CC anaphylaxis or hypersensitivity responses, drug allergies, eczema, atopic
CC dermatitis, allergic contact dermatitis, urticaria, vasculitis, allergic
CC rhinitis; autoimmune diseases, selected from arthritis, osteoarthritis,
CC multiple sclerosis, systemic lupus erythematosus, diabetes mellitus, and
CC glomerulonephritis; graft rejection chosen from allograft rejection and
CC graft vs host disease; and other diseases in which undesired inflammatory
CC responses are to be inhibited preferably, Alzheimer's disease,
CC encephalitis, and meningitis. The present sequence represents a DNA
CC encoding a Faecalibacterium prausnitzii protein (ZP05614546.1) which is
CC used for treating or preventing inflammatory diseases in the invention.
XX
SQ Sequence 408 BP; 106 A; 117 C; 95 G; 90 T; 0 U; 0 Other;
Query Match 100.0%; Score 408; Length 408;
Best Local Similarity 100.0%;
Matches 408; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGATGATGCCTGCAAACTACTCTGTTATCGCAGAGAACGAAATGACCTACGTCAACGGT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 ATGATGATGCCTGCAAACTACTCTGTTATCGCAGAGAACGAAATGACCTACGTCAACGGT 60
Qy 61 GGCGCTAACTTCATCGACGCTATCGGCGCTGTTACCGCTCCTATCTGGACTCTGGACAAC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GGCGCTAACTTCATCGACGCTATCGGCGCTGTTACCGCTCCTATCTGGACTCTGGACAAC 120
Qy 121 GTTAAGACCTTCAACACCAACATCGTGACTCTGGTTGGCAACACCTTCCTGCAGTCCACC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GTTAAGACCTTCAACACCAACATCGTGACTCTGGTTGGCAACACCTTCCTGCAGTCCACC 180
Qy 181 ATTAACCGCACCATCGGTGTCCTGTTCAGCGGCAACACCACCTGGAAGGAAGTCGGCAAC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ATTAACCGCACCATCGGTGTCCTGTTCAGCGGCAACACCACCTGGAAGGAAGTCGGCAAC 240
Qy 241 ATCGGCAAGAACCTGTTCGGCACCAATGTTAAGGGCAACCCGATCGAGAAGAACAACTTT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 ATCGGCAAGAACCTGTTCGGCACCAATGTTAAGGGCAACCCGATCGAGAAGAACAACTTT 300
Qy 301 GGTGACTATGCTATGAACGCTCTGGGCATTGCTGCTGCTGTCTACAACCTGGGCGTGGCT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GGTGACTATGCTATGAACGCTCTGGGCATTGCTGCTGCTGTCTACAACCTGGGCGTGGCT 360
Qy 361 CCCACCAAGAACACCGTCAAGGAGACTGAGGTTAAGTTCACTGTCTAA 408
||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 CCCACCAAGAACACCGTCAAGGAGACTGAGGTTAAGTTCACTGTCTAA 408
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SATYENDRA K. SINGH whose telephone number is (571)272-8790. The examiner can normally be reached M-F 8:00- 5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, LOUISE W HUMPHREY can be reached at 571-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SATYENDRA K SINGH/Primary Examiner, Art Unit 1657
SATYENDRA K. SINGH
Primary Examiner
Art Unit 1657