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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 03/19/2026 has been entered.
Claims 2-4 and 19-20 were previously canceled by the applicants.
Claims 6, 17, 22 and 23 have now been canceled by applicant’s current claim amendments. It is noted that claim 17 was directed to the withdrawn product of Group II (see CTRS paper dated 02/27/2025, page 3).
Claim 24 (new, withdrawn), and claims 25 and 26 (taken under elected Group I) have been newly presented.
Claims 1, 5, 7-16, 18, 21 and 24-26 as currently amended are pending in this application.
Claims 18, 21 and 24 (non-elected product of Groups III) remain withdrawn.
Claims 1, 5, 7-16, 25 and 26 (elected invention of Group I, without traverse; directed to “A method or treating an irradiation-induced intestinal damage in a subject…”) have been examined on their merits in this action hereinafter.
Priority
This application is a 371 of PCT/US2020/058105 (filed on 10/30/2020), which claims domestic benefit from a US PRO 62/929,146 filed on 11/01/2019.
Claim Objections -Withdrawn
In view of current amendment to claim 1, the claim objection (for typographical error) as previously made by the examiner has been withdrawn.
The following contains new grounds of objections/rejections over pending claims as currently presented by applicants.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
1. Claim 8 (as currently recited) is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 8 is reproduced as follows:
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It is to be noted that instant claim 8 directly depends from independent claim 1, which has now been amended by applicants to delete the limitations of “Interleukin-22 (IL-22) and/or” (see claim 1, line 5), and the recited SEQ ID NO: 2 as per instant disclosure comprises the specific polynucleotide sequence for IL-22 (see SPEC, p. 14, line 8; also see previously provided sequence homology for SEQ ID NO: 2 reproduced hereinbelow):
ALIGNMENTS- SEQ ID NO: 2 (instant claim 8)
RESULT 1 (GenEmbl database)
BC116235
LOCUS BC116235 678 bp mRNA linear ROD 04-OCT-2006
DEFINITION Mus musculus interleukin 22, mRNA (cDNA clone MGC:143650
IMAGE:40091712), complete cds.
ACCESSION BC116235
VERSION BC116235.2
KEYWORDS MGC.
SOURCE Mus musculus (house mouse)
ORGANISM Mus musculus
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE 1 (bases 1 to 678)
AUTHORS Strausberg,R.L., Feingold,E.A., Grouse,L.H., Derge,J.G.,
Klausner,R.D., Collins,F.S., Wagner,L., Shenmen,C.M., Schuler,G.D.,
Altschul,S.F., Zeeberg,B., Buetow,K.H., Schaefer,C.F., Bhat,N.K.,
Hopkins,R.F., Jordan,H., Moore,T., Max,S.I., Wang,J., Hsieh,F.,
Diatchenko,L., Marusina,K., Farmer,A.A., Rubin,G.M., Hong,L.,
Stapleton,M., Soares,M.B., Bonaldo,M.F., Casavant,T.L.,
Scheetz,T.E., Brownstein,M.J., Usdin,T.B., Toshiyuki,S.,
Carninci,P., Prange,C., Raha,S.S., Loquellano,N.A., Peters,G.J.,
Abramson,R.D., Mullahy,S.J., Bosak,S.A., McEwan,P.J.,
McKernan,K.J., Malek,J.A., Gunaratne,P.H., Richards,S.,
Worley,K.C., Hale,S., Garcia,A.M., Gay,L.J., Hulyk,S.W.,
Villalon,D.K., Muzny,D.M., Sodergren,E.J., Lu,X., Gibbs,R.A.,
Fahey,J., Helton,E., Ketteman,M., Madan,A., Rodrigues,S.,
Sanchez,A., Whiting,M., Madan,A., Young,A.C., Shevchenko,Y.,
Bouffard,G.G., Blakesley,R.W., Touchman,J.W., Green,E.D.,
Dickson,M.C., Rodriguez,A.C., Grimwood,J., Schmutz,J., Myers,R.M.,
Butterfield,Y.S., Krzywinski,M.I., Skalska,U., Smailus,D.E.,
Schnerch,A., Schein,J.E., Jones,S.J. and Marra,M.A.
CONSRTM Mammalian Gene Collection Program Team
TITLE Generation and initial analysis of more than 15,000 full-length
human and mouse cDNA sequences
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 99 (26), 16899-16903 (2002)
PUBMED 12477932
REFERENCE 2 (bases 1 to 678)
CONSRTM NIH MGC Project
TITLE Direct Submission
JOURNAL Submitted (03-MAY-2006) National Institutes of Health, Mammalian
Gene Collection (MGC), Bethesda, MD 20892-2590, USA
REMARK NIH-MGC Project URL: http://mgc.nci.nih.gov
COMMENT On Oct 4, 2006 this sequence version replaced BC116235.1.
Contact: MGC help desk
Email: cgapbs-r\@mail.nih.gov
Tissue Procurement: Baylor Human Genome Sequencing Center
cDNA Library Preparation: Baylor Human Genome Sequencing Center
cDNA Library Arrayed by: The I.M.A.G.E. Consortium (LLNL)
DNA Sequencing by: Sequencing Group at the Stanford Human Genome
Center, Stanford University School of Medicine, Stanford, CA 94305
Web site: http://www-shgc.stanford.edu
Contact: (Dickson, Mark) mcd\@paxil.stanford.edu
Dickson, M., Schmutz, J., Grimwood, J., Rodriquez, A., and Myers,
R. M.
Clone distribution: MGC clone distribution information can be found
through the I.M.A.G.E. Consortium/LLNL at: http://image.llnl.gov
Series: IRAM Plate: 22 Row: k Column: 16.
FEATURES Location/Qualifiers
source 1..678
/organism="Mus musculus"
/mol_type="mRNA"
/db_xref="taxon:10090"
/clone="MGC:143650 IMAGE:40091712"
/tissue_type="PCR rescued clones"
/clone_lib="NIH_MGC_284"
/note="Vector: pCR-Blunt II-TOPO; Clone identification
sequence tag: CTTATCTT sequenced from the reverse primer"
gene 1..678
/gene="Il22"
/gene_synonym="IL-22"
/gene_synonym="IL-TIF"
/db_xref="GeneID:50929"
/db_xref="MGI:MGI:1355307"
CDS 24..563
/gene="Il22"
/gene_synonym="IL-22"
/gene_synonym="IL-TIF"
/codon_start=1
/product="interleukin 22"
/protein_id="AAI16236.1"
/db_xref="GeneID:50929"
/db_xref="MGI:MGI:1355307"
/translation="MAVLQKSMSFSLMGTLAASCLLLIALWAQEANALPVNTRCKLEV
SNFQQPYIVNRTFMLAKEASLADNNTDVRLIGEKLFRGVSAKDQCYLMKQVLNFTLED
VLLPQSDRFQPYMQEVVPFLTKLSNQLSSCHISGDDQNIQKNVRRLKETVKKLGESGE
IKAIGELDLLFMSLRNACV
Query Match 96.8%; Score 518.6; Length 678;
Best Local Similarity 99.1%;
Matches 532; Conservative 0; Mismatches 4; Indels 1; Gaps 1;
Qy 1 ATGGCTGTCCTGCAGAAATCTATGAGTTTTTCCCTTATGGGGACTTTGGCCGCCAGCTGC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 24 ATGGCTGTCCTGCAGAAATCTATGAGTTTTTCCCTTATGGGGACTTTGGCCGCCAGCTGC 83
Qy 61 CTGCTTCTCATTGCCCTGTGGGCCCAGGAGGCAAATGCGCTGCCCATCAACACCCGGTGC 120
||||||||||||||||||||||||||||||||||||||||||||| ||||||||||||||
Db 84 CTGCTTCTCATTGCCCTGTGGGCCCAGGAGGCAAATGCGCTGCCCGTCAACACCCGGTGC 143
Qy 121 AAGCTTGAGGTGTCCAACTTCCAGCAGCCGTACATCGTCAACCGCACCTTTATGCTGGCC 180
||||||||||||||||||||||||||||| ||||||||||||||||||||||||||||||
Db 144 AAGCTTGAGGTGTCCAACTTCCAGCAGCCATACATCGTCAACCGCACCTTTATGCTGGCC 203
Qy 181 AAGGAGGCCAGCCTTGCAGATAACAACACAGACGTCCGGCTCATCGGGGAGAAACTGTT- 239
|||||||||||||||||||||||||||||||| ||||||||||||||||||||||||||
Db 204 AAGGAGGCCAGCCTTGCAGATAACAACACAGATGTCCGGCTCATCGGGGAGAAACTGTTC 263
Qy 240 CGAGGAGTCAGTGCTAAGGATCAGTGCTACCTGATGAAGCAGGTGCTCAACTTCACCCTG 299
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 264 CGAGGAGTCAGTGCTAAGGATCAGTGCTACCTGATGAAGCAGGTGCTCAACTTCACCCTG 323
Qy 300 GAAGACGTTCTGCTCCCCCAGTCAGACAGGTTCCAGCCCTACATGCAGGAGGTGGTGCCT 359
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 324 GAAGACGTTCTGCTCCCCCAGTCAGACAGGTTCCAGCCCTACATGCAGGAGGTGGTGCCT 383
Qy 360 TTCCTGACCAAACTCAGCAATCAGCTCAGCTCCTGTCACATCAGCGGTGACGACCAGAAC 419
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 384 TTCCTGACCAAACTCAGCAATCAGCTCAGCTCCTGTCACATCAGCGGTGACGACCAGAAC 443
Qy 420 ATCCAGAAGAATGTCAGAAGGCTGAAGGAGACAGTGAAAAAGCTTGGAGAGAGTGGAGAG 479
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 444 ATCCAGAAGAATGTCAGAAGGCTGAAGGAGACAGTGAAAAAGCTTGGAGAGAGTGGAGAG 503
Qy 480 ATCAAAGCGATTGGGGAACTGGACCTGCTGTTTATGTCTCTGAGAAATGCTTGCGTC 536
||||| |||||||||||||||||||||||||||||||||||||||||||||||||||
Db 504 ATCAAGGCGATTGGGGAACTGGACCTGCTGTTTATGTCTCTGAGAAATGCTTGCGTC 560
Therefore, instant claim 8 as presented does not appear to further limit the scope of the independent claim 1 from which it depends from, and in fact it broadens the scope to encompass both IL-22 and interferon-beta. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Appropriate correction is required.
NOTE: 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.
Claim Rejections - 35 USC § 103 – New Grounds
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
1. Claims 1, 5, 7, 9-12, 15, 16, 25 and 26 (as amended/newly presented) are rejected under 35 U.S.C. 103 as being unpatentable over Van Den Brink et al (US 2016/0287670 A1; USPAT cited in IDS dated 04/29/2022) taken with Van Pijkeren et al (US 10,376,563 B1; USPAT cited in IDS dated 12/12/2022), Pal et al (2018; NPL cited as ref. [U] on PTO 892 form) and Barber (US 2019/0314429 A1; previously made of record by examiner).
Claim 1 (as currently amended) is directed to “A method of treating an irradiation-induced intestinal damage in a subject comprising administering to the subject a therapeutically effective amount of a gastrointestinal tract (GI) bacterium, wherein the GI bacterium is Escherichia coli or Lactobacillus reuteri and wherein the bacterium comprises a vector comprising a polynucleotide that encodes b).”
See also limitations of dependent claims 5, 7, 9-12, 15, 16 and new claims 25-26, as currently amended/presented.
Van Den Brink et al (2016) disclose the method of treating an Total Body Irradiation (TBI)-Induced intestinal damage in a subject by administering bacteria expressing anti-inflammatory cytokines {method for promoting the recovery/regeneration of gastrointestinal epithelial cells in a subject following damage to the epithelial lining of the gastrointestinal (GI) tract, the method comprising contacting intestinal stem cells of the subject with IL-22, Para. [0009]; a subject may be immunocompromised ... [e]xamples of immunocompromised subjects include subjects that have any of the following conditions, chemotherapy, exposure to radiation, deliberate irradiation, Para. [0046]; [t]he present invention provides methods and compositions for the use of IL-22 for treating conditions of intestinal injury, Para. [0089])} comprising administering to the subject a therapeutically effective amount of a gastrointestinal tract (GI) bacterium (using IL-22 cytokine-expressing bacteria, Para. [0157]; IL-22 was administrated post-HCT using lacto-22s and lacto-22a bacteria of the present inventions as described herein. Para. [0165]), wherein the bacterium comprises a vector comprising a polynucleotide that encodes IL-22 {[a] nucleic acid comprising a nucleotide sequence encoding IL-22 can be inserted into a replicable vector for gene cloning or protein expression, Para. [0095]; using IL-22 expressing bacteria, Para. [0157]}; wherein regarding the particular cytokine, IL-22 employed in the method, they disclose that “the term “IL-22 polypeptide' or “IL-22” or “IL22” or “IL-22 protein” refers to a biologically active polypeptide capable of producing the biological activity as described herein. IL-22 of the present invention includes but not limited to human IL-22, recombinant human IL-22, murine IL-22 and/or recombinant murine IL-22..,” (Para [0014]-[0016], also specific polypeptide sequences referred in the cited references therein, for instance); wherein they disclose that the GI bacterium is a species of Lactobacillus genus that are administered using oral gavage (using IL-22 expressing bacteria, Para. [0157]; IL-22 was administrated post-HCT using lacto-22s and lacto-22a bacteria of the present inventions as described herein. Para. [0165]; lactobacilli expressing IL-22, Para. [0014]); wherein the administration is done post-HCT, using oral gavage of 108 to 109 Lactobacillus paracasei (wild-type, or lacto-22s, or lacto-22a resuspended in PBS; para [0165]); wherein the GI bacterium resides in an area of a colon or a small intestine following administration (entire para [0163], “the inventors made two strains of Lactobacillus paracasei that constitutively produced IL-22…One strain produces secreted IL-22 (lacto 22s) while the other strain produced IL-22 anchored to the bacterial cell surface (lacto-22a)”); and wherein the method is suitable for cancer patients (including cancers of blood or bone marrow) that are undergoing stem cell transplantations such as “allogeneic HSCT” (para [0025]…in these cases, the recipient’s immune system is usually destroyed with radiation or chemotherapy before the transplantation. Infection and graft-versus-host disease is a major complication of HSCT); wherein the treatment with IL-22+ lactobacilli was shown to reduce the intestinal tissue damage (see para [0216]-[0218], for instance) in experimental GVHD model.
Van Den Brink et al also disclose that “cytokine” refers to a protein or glycoprotein that is used in an organism as signaling compounds. It is intended to include homologues and synthetic versions. Examples include IL-22, IL-23, IL-21, the IL-10 family, IL-7, the interferon (IFN) family, CC chemokines, CXC chemokines, and the like” (see para [0054]). Thus, although Van Den Brink et al do not explicitly exemplify all the above listed cytokine members per se, they nevertheless suggest the use of certain cytokines, including cytokine from interferon family, as being a therapeutic modality for treating radiation-induced intestinal inflammatory conditions.
However, the treatment method wherein- (1) the GI bacterium is Escherichia coli or Lactobacillus reuteri (instant claim 1, as currently amended); (2) the GI bacterium comprises a vector expressing and secreting interferon-beta (IFN-b; see instant claims 7 reciting SEQ ID NO: 4 for known mouse interferon-beta gene sequence; see sequence homology discussed below), have not been explicitly exemplified by the method disclosed by Van Den Brink et al, as discussed above (although they do suggest the use of cytokine members from the interferon family; see Van Den Brink et al, para [0054]).
Van Pijkeren et al (2019) disclose methods for systemically introducing a polypeptide in the bloodstream of a subject (see Title, Abstract), wherein the methods of the invention include administering into the gastrointestinal tract of a subject a probiotic, food grade bacterium (see column 4, lines 54-59) configured to express and produce and secrete/release the polypeptide, wherein the bacterium is administered in an amount effective to introduce the polypeptide in the bloodstream of the subject, preferably in a detectable amount, wherein the microorganisms of the invention include lactic acid bacteria, such as Lactobacillus reuteri, that comprise a recombinant gene configured to express a polypeptide to be systemically introduced (Abstract, Summary of the invention; column 10, 3rd paragraph, and claims, for instances); wherein the exemplary classes of cytokines include interleukins, lymphokines, monokines, interferons (IFNs), colony stimulating factors (CSFs), including recombinant IL-22 polypeptides, and interferon members including IFN-b (see column 8, 2nd paragraph, and claim 8, for instance); wherein they disclose and explicitly state that L. reuteri can be used to systemically deliver polypeptides other than IL-22 by editing the plasmid and replacing the open reading frame of the gene with any polypeptide of interest (see column 21, 2nd paragraph, for instance); wherein they show that L. reuteri displayed an “exceptionally low mutation rate”, particularly compared to the other tested probiotic microbes (see column 15, section “Mutation Rate”, for instance), and is capable of systemically delivering any polypeptide of interest without the bacterium itself being delivered systemically (column 21, lines 14-16).
Pal et al (2018) disclose expression of a therapeutic cytokine, recombinant human interferon-beta protein (rhIFN-b) using prokaryotic host cell expression system comprising Escherichia coli cells (comparative expression in E. coli DE3 versus E. coli SE1 cells; see Abstract, Introduction 1st paragraph; and Figures 1, 3-5); wherein they demonstrate and state that “…compared to BL21(DE3) cells, the SE1 cells expressing rhIFN-β protein can be cultivated in the medium without antibiotic and provide increased stability of recombinant plasmid and higher expression yield of rhIFN-β protein. This system can be used for the production of rhIFN-β proteins for biomedical applications”; wherein they disclose an effective and safe way to produce rhIFN-b protein which can be scaled up for the large -scale production for various biomedical applications (see section “Discussion”, p. 6, left column). Although, the cited reference does not specifically disclose the use of E. coli host cells comprising the rhIFN-b for administration into a subject with irradiation-induced intestinal damage, it nevertheless practically demonstrates the use of bacterial host, Escherichia coli SE1 cells for cloning, expression and secretion of functional therapeutic and anti-inflammatory cytokine, rhIFN-b protein.
Barber (2019), while teaching cancer treatment based on the functional activity of simulator of interferon genes (STING) or cGAS in the cancer cells (see Abstract, [0007]-[0008], Summary [0010], [0043], [0063]-[0065], Fig. 16E, for instance), including colitis-associated cancer (CAC), disclose the relationships of related host defense cytokines especially IL-22 and interferon-beta (IFN-b; see [0023], for instance), wherein the enhanced secretion of these cytokines (via oncolytic virus treatment that induce immune response via STING or cGAS; see claims on page 30, for instance) provide positive outcome of oncolytic therapy of cancers such as colorectal cancer, CAC and melanoma; and wherein STING appears to play a pivotal sensor role in controlling a variety of inflammation driven events (including Inflammatory Bowel Disease, IBD), and promotes elimination of damaged intestinal epithelial cells, and help in tissue wound repair process in the gut (see [0065], [0132]-[0133], [0139], [0172]-[0173], for instance). Thus, Barber discloses the direct role of cytokines including interleukin-22 and interferon-beta in the host immune defense and/or wound repair mechanisms in the gastrointestinal (GI) tissues.
Thus, given the detailed disclosure for the gastrointestinal host bacterium (GI bacterium) including food grade probiotic bacterium Lactobacillus reuteri for cloning and expression of desired secreted cytokines such as IL-22 and IFN-b (Van Pijkeren et al, as discussed above), for the suitable host cells including Escherichia coli (Pal et al, discussed above for expressing therapeutic cytokine rhIFN-b), and for the direct relationship and role of host defense related cytokines including IL-22 and IFN-b in host immune response and tissue repair, including GI tract tissues (Barber, as discussed above), it would have been obvious to an artisan of ordinary skill in the art to modify the method disclosed by Van Den Brink et al such that it employs GI bacterium as host cells (such as probiotic Lactobacillus reuteri or Escherichia coli) that comprise suitable vector with polynucleotides that encode and express therapeutic cytokine(s) such as IL-22 or IFN-b, or a combination thereof, as both have been shown to reduce inflammation in the GI tract tissues, and help repair wound or damage in the gut of a subject in need thereof, as already disclosed and/or demonstrated by Van der Brink et al. Since, the polynucleotide sequences of the cytokines from various mammalian sources have already been known in the art (see Pal et al Figure 2; and the sequence homology below for SEQ ID NO: 4), such modification in the type of GI bacterial host cells, and/or expression vectors comprising said cytokines (or combinations thereof) for treating irradiation-induced intestinal damage in a subject in need would have been obvious and/or fully contemplated by an artisan of ordinary skill in the art, unless evidence and/or data provided on record to the contrary (which is currently lacking in the disclosure of record; see for instances, SPEC p. 7, paragraphs 2-3 and 5).
Also, since the physiological role of both therapeutic cytokines IL-22 and IFN-b have been specifically disclosed and/or suggested in various cancers (see also teachings/suggestions from Barber, for instance), an artisan in the art would have fully contemplated such treatment for damage induced by radiation during chemotherapy for cancers including ovarian cancer, or any other colon, abdominal or any other cancerous tissues. Since, the dose levels of the therapeutically effective composition comprising particular cytokine and specific bacterium host would be different depending on the specific condition and/or damage, or the type of GI tissue in the subject in need, such dose levels of the GI bacterium expressing and secreting IL-22 or IFN-b cytokines would be considered optimizable result-effective variables, and an artisan in the art would be able to adjust depending on the need at hand (see teachings from Van Den Brink et al, as discussed above). Therefore, the claimed treatment process fails to distinguish itself over the combined teachings and/or suggestions from the cited prior art of Van Den Brink et al when taken with Van Pijkeren et al, Pal et al, and Barber, as discussed above.
2. Claims 13-14 (as presented) are/remain rejected under 35 U.S.C. 103 as being unpatentable over Van Den Brink et al (US 2016/0287670 A1; USPAT cited in IDS dated 04/29/2022) taken with Van Pijkeren et al (US 10,376,563 B1; USPAT cited in IDS dated 12/12/2022), Pal et al (2018; NPL cited as ref. [U] on PTO 892 form) and Barber (US 2019/0314429 A1; Previously made of record), as applied to claims 1, 5, 7, 9-12, 15, 16, 25 and 26 above, and further in view of Wei et al (1st Feb. 2018; Scientific Report, 8:2072; NPL cited in IDS dated 12/12/2022, citation no. 112).
Claim 13 is directed to “The method of claim 1, further comprising administering to the subject a therapeutically effective amount of an irradiation mitigator.”
(see also limitations of the amended claim 14, as currently presented)
The combined teachings and/or suggestions for the method of claims 1, 5, 7, 9-12, 15, 16, 25 and 26 have been discussed above in details for the cited prior art references of Van Den Brink et al taken with Van Pijkeren et al, Pal et al, and Barber, and have been further relied upon in the same manner hereinafter.
However, the use of a “radiation mitigator” in combination with the GI bacterium composition comprising a vector having polynucleotide that encodes IFN-b (see instant claims 13 and 14), have not been specifically disclosed by the cited references as discussed above.
Wei et al (2018) disclose the fact that an antioxidant GS-nitroxide JP4-039 (given at 5 to 20 mg/kg dose, once 24 hours after 9-10 Gy total body irradiation (TBI)) significantly improves mouse survival, and the recovery of intestinal barrier, differentiation and stem cell functions (see title and Abstract, Fig. 1-2 and 5-6, in particular), wherein the GI-protective effects are associated with rapid and selective induction of tight junction proteins and anti-inflammatory cytokines including IL-17a, IL-22, and thus provides an effective strategy to enhance intestinal stem cell recovery and regeneration after accidental or medical exposures, or TBI.
Thus, to a person of ordinary skill in the art, it would have been obvious to include such radiation mitigators, especially for the method of treating radiation-induced intestinal damage using anti-inflammatory cytokines in a subject in need thereof as disclosed and/or suggested by Wei et al, in the composition comprising GI bacterium as taught by the combined disclosure from Van Den Brink et al taken with Van Pijkeren et al, Pal et al and Barber, as discussed in details above. An artisan in the art would be motivated for such modification in the treatment method, as Wei et al specifically demonstrate the significant survival benefits in experimental animals that have been exposed to total body irradiation (TBI) with special reference to intestinal barrier and stem cell recovery in the irradiated mice (see Wei et al, Fig. 1-2, for instance).
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 ALIGNMENT RESULTS
ALIGNMENTS- SEQ ID NO: 4 (Instant claim 7)
RESULT 1 (GenEmbl database)
BC119395
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
LOCUS BC119395 615 bp mRNA linear ROD 09-AUG-2006
DEFINITION Mus musculus interferon beta 1, fibroblast, mRNA (cDNA clone
MGC:155711 IMAGE:8734144), complete cds.
ACCESSION BC119395
VERSION BC119395.1
KEYWORDS MGC.
SOURCE Mus musculus (house mouse)
ORGANISM Mus musculus
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE 1 (bases 1 to 615)
AUTHORS Strausberg,R.L., Feingold,E.A., Grouse,L.H., Derge,J.G.,
Klausner,R.D., Collins,F.S., Wagner,L., Shenmen,C.M., Schuler,G.D.,
Altschul,S.F., Zeeberg,B., Buetow,K.H., Schaefer,C.F., Bhat,N.K.,
Hopkins,R.F., Jordan,H., Moore,T., Max,S.I., Wang,J., Hsieh,F.,
Diatchenko,L., Marusina,K., Farmer,A.A., Rubin,G.M., Hong,L.,
Stapleton,M., Soares,M.B., Bonaldo,M.F., Casavant,T.L.,
Scheetz,T.E., Brownstein,M.J., Usdin,T.B., Toshiyuki,S.,
Carninci,P., Prange,C., Raha,S.S., Loquellano,N.A., Peters,G.J.,
Abramson,R.D., Mullahy,S.J., Bosak,S.A., McEwan,P.J.,
McKernan,K.J., Malek,J.A., Gunaratne,P.H., Richards,S.,
Worley,K.C., Hale,S., Garcia,A.M., Gay,L.J., Hulyk,S.W.,
Villalon,D.K., Muzny,D.M., Sodergren,E.J., Lu,X., Gibbs,R.A.,
Fahey,J., Helton,E., Ketteman,M., Madan,A., Rodrigues,S.,
Sanchez,A., Whiting,M., Madan,A., Young,A.C., Shevchenko,Y.,
Bouffard,G.G., Blakesley,R.W., Touchman,J.W., Green,E.D.,
Dickson,M.C., Rodriguez,A.C., Grimwood,J., Schmutz,J., Myers,R.M.,
Butterfield,Y.S., Krzywinski,M.I., Skalska,U., Smailus,D.E.,
Schnerch,A., Schein,J.E., Jones,S.J. and Marra,M.A.
CONSRTM Mammalian Gene Collection Program Team
TITLE Generation and initial analysis of more than 15,000 full-length
human and mouse cDNA sequences
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 99 (26), 16899-16903 (2002)
PUBMED 12477932
REFERENCE 2 (bases 1 to 615)
CONSRTM NIH MGC Project
TITLE Direct Submission
JOURNAL Submitted (10-JUL-2006) National Institutes of Health, Mammalian
Gene Collection (MGC), Bethesda, MD 20892-2590, USA
REMARK NIH-MGC Project URL: http://mgc.nci.nih.gov
COMMENT Contact: MGC help desk
Email: cgapbs-r\@mail.nih.gov
Tissue Procurement: Ambion
cDNA Library Preparation: British Columbia Cancer Research Center
cDNA Library Arrayed by: The I.M.A.G.E. Consortium (LLNL)
DNA Sequencing by: Genome Sequence Centre,
BC Cancer Agency, Vancouver, BC, Canada
info\@bcgsc.bc.ca
Martin Hirst, Thomas Zeng, Ryan Morin, Michelle Moksa, Johnson
Pang, Diana Mah, Jing Wang, Kieth Fichter, Eric Chuah, Allen
Delaney, Rob Kirkpatrick, Agnes Baross, Sarah Barber, Mabel
Brown-John, Steve S. Chand, William Chow, Ryan Babakaiff, Dave
Wong, Corey Matsuo, Jaclyn Beland, Susan Gibson, Luis delRio, Ruth
Featherstone, Malachi Griffith, Obi Griffith, Ran Guin, Nancy Liao,
Kim MacDonald, Mike R. Mayo, Josh Moran, Diana Palmquist, JR
Santos, Duane Smailus, Jeff Stott, Miranda Tsai, George Yang,
Jacquie Schein, Asim Siddiqui,Steven Jones, Rob Holt, Marco Marra.
Clone distribution: MGC clone distribution information can be found
through the I.M.A.G.E. Consortium/LLNL at: http://image.llnl.gov
Series: IRCK Plate: 2 Row: P Column: 14.
FEATURES Location/Qualifiers
source 1..615
/organism="Mus musculus"
/mol_type="mRNA"
/db_xref="taxon:10090"
/clone="MGC:155711 IMAGE:8734144"
/tissue_type="Brain,thymus,testicle,kidney,spleen,liver,
heart,lung,ovary,embryo - PCR rescued clones"
/clone_lib="NIH_MGC_389"
/lab_host="DH10B"
/note="Vector: pCR4-TOPO; Clone identification sequence
tag: TGCTACCC"
gene 1..615
/gene="Ifnb1"
/gene_synonym="IFNB"
/db_xref="GeneID:15977"
/db_xref="MGI:MGI:107657"
CDS 21..569
/gene="Ifnb1"
/gene_synonym="IFNB"
/codon_start=1
/product="interferon beta 1, fibroblast"
/protein_id="AAI19396.1"
/db_xref="GeneID:15977"
/db_xref="MGI:MGI:107657"
/translation="MNNRWILHAAFLLCFSTTALSINYKQLQLQERTNIRKCQELLEQ
LNGKINLTYRADFKIPMEMTEKMQKSYTAFAIQEMLQNVFLVFRNNFSSTGWNETIVV
RLLDELHQQTVFLKTVLEEKQEERLTWEMSSTALHLKSYYWRVQRYLKLMKYNSYAWM
VVRAEIFRNFLIIRRLTRNFQN
Query Match 100.0%; Score 546; Length 615;
Best Local Similarity 100.0%;
Matches 546; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ATGAACAACAGGTGGATCCTCCACGCTGCGTTCCTGCTGTGCTTCTCCACCACAGCCCTC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 ATGAACAACAGGTGGATCCTCCACGCTGCGTTCCTGCTGTGCTTCTCCACCACAGCCCTC 80
Qy 61 TCCATCAACTATAAGCAGCTCCAGCTCCAAGAAAGGACGAACATTCGGAAATGTCAGGAG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 TCCATCAACTATAAGCAGCTCCAGCTCCAAGAAAGGACGAACATTCGGAAATGTCAGGAG 140
Qy 121 CTCCTGGAGCAGCTGAATGGAAAGATCAACCTCACCTACAGGGCGGACTTCAAGATCCCT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 CTCCTGGAGCAGCTGAATGGAAAGATCAACCTCACCTACAGGGCGGACTTCAAGATCCCT 200
Qy 181 ATGGAGATGACGGAGAAGATGCAGAAGAGTTACACTGCCTTTGCCATCCAAGAGATGCTC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 201 ATGGAGATGACGGAGAAGATGCAGAAGAGTTACACTGCCTTTGCCATCCAAGAGATGCTC 260
Qy 241 CAGAATGTCTTTCTTGTCTTCAGAAACAATTTCTCCAGCACTGGGTGGAATGAGACTATT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 261 CAGAATGTCTTTCTTGTCTTCAGAAACAATTTCTCCAGCACTGGGTGGAATGAGACTATT 320
Qy 301 GTTGTACGTCTCCTGGATGAACTCCACCAGCAGACAGTGTTTCTGAAGACAGTACTAGAG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 321 GTTGTACGTCTCCTGGATGAACTCCACCAGCAGACAGTGTTTCTGAAGACAGTACTAGAG 380
Qy 361 GAAAAGCAAGAGGAAAGATTGACGTGGGAGATGTCCTCAACTGCTCTCCACTTGAAGAGC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 381 GAAAAGCAAGAGGAAAGATTGACGTGGGAGATGTCCTCAACTGCTCTCCACTTGAAGAGC 440
Qy 421 TATTACTGGAGGGTGCAAAGGTACCTTAAACTCATGAAGTACAACAGCTACGCCTGGATG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 441 TATTACTGGAGGGTGCAAAGGTACCTTAAACTCATGAAGTACAACAGCTACGCCTGGATG 500
Qy 481 GTGGTCCGAGCAGAGATCTTCAGGAACTTTCTCATCATTCGAAGACTTACCAGAAACTTC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 501 GTGGTCCGAGCAGAGATCTTCAGGAACTTTCTCATCATTCGAAGACTTACCAGAAACTTC 560
Qy 541 CAAAAC 546
||||||
Db 561 CAAAAC 566
Examiner’s Response to Arguments
Applicant’s arguments with respect to pending claim(s) as currently amended/presented (see REM dated 03/19/2026; p. 5-7) have been considered but are moot in view of the new grounds of objections/rejections made in this office action, as discussed in details above.
Conclusion
NO claims are currently allowed.
Pertinent Prior Art:
1. Strausberg R. L. et al. (2002; previously made of record by examiner)- “Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences; Mammalian Gene Collection (MGC) Program team”, PNAS, Dec. 2002, vol. 99, no. 26, pages 16899-16903 (disclose the mammalian genes and cDNA sequences including for the interferon-beta and interleukin-22 versions known in the prior art).
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SATYENDRA K. SINGH
Primary Examiner
Art Unit 1657
/SATYENDRA K SINGH/Primary Examiner, Art Unit 1657