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 02/12/2026 is duly acknowledged.
Claims 1-17 and 19-21 were previously canceled by applicants (include withdrawn invention of Group I).
Claims 23-28 were newly presented for examination.
No claims have been currently amended.
Claims 18 and 22-28 (taken as elected invention of Group II, without traverse; directed to “A population of therapeutic bacteria…”) have been examined on their merits in this action hereinafter.
Priority
This application is a 371 of PCT/US2020/051661 (filed on 09/18/2020), which claims domestic benefit from a US PRO 62/902,327 filed on 09/18/2019.
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- Maintained
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 18 and 22-28 (as presented) remain rejected under 35 U.S.C. 103 as being unpatentable over Barrangou et al (US 2011/0002889 A1; previously of record; see applicant’s IDS dated 10/11/2022) taken with Stuer-Lauridsen et al (US 2008/0317903 A1; cited in applicant’s IDS dated 10/11/2022) and Cornuault et al (2018; NPL previously cited by examiner on record).
Claim 18 (as presented) is directed to “A population the therapeutic bacteria being engineered to contain:
at least one clustered regularly interspaced short palindromic repeats (CRISPR)-Casassociated with a disease, disorder, or condition associated with
wherein the distinct target bacteriophage has been demonstrated to deplete a population
wherein the therapeutic bacteria are resistant to infection by the distinct target the subject
It is noted that instant claim neither requires any specific “distinct target” bacteriophage sequence, nor any particular “therapeutic bacteria” per se.
See also limitations of dependent claims 22-28 as currently presented.
Barrangou et al (2011), while teaching cultures with improved phage resistance (see Title, Abstract, Summary of the invention, and Claims), disclose a therapeutic product composition (probiotic and dietary supplement compositions, including for health and pharmaceutical use; see paragraphs [0006], [0378], [0412], for instances) comprising an engineered population of therapeutic bacteria (bacteriophage-resistant strain produced through genetic modification; see paragraphs [0004]-[0006]) that (i) are non-pathogenic and commensal in a subject to be administered (probiotic bacteria including strains used for food fermentation and pharmaceutical use; i.e. non-pathogenic and commensal in a subject to be administered; see paragraphs [0006], [0377]-[0378], for instance); and (ii) are resistant to one or more target bacteriophages (cells produced using methods that confer resistance to a bacteriophage; see paragraphs [0006], [0305]-[0306], [0419], for instance); wherein the therapeutic bacteria each comprise a clustered regularly interspaced short palindromic repeats (CRISPR) spacer that targets the one or more target bacteriophages (engineering the CRISPR loci in the cell such that they comprise one or more CRISPR spacers complementary or homologous to sequences from the bacteriophage; see paragraphs [0129], [0305]-[0306], claims 23-27, for instance); wherein suitable therapeutic bacteria include probiotic, lactic acid bacteria such as Bifidobacterium species, Lactococcus species, and Lactobacillus species (see paragraphs [0059], [0377], for instance); wherein the target bacteriophage (that infect the bacterial strains) may include bacteriophages from families such as myoviridae, podoviridae, siphoviridae, etc. (i.e. phage families of the order Caudovirales; see [0004], [0059], [0292], claims 7-8, for instance).
However, the population of engineered therapeutic bacteria resistant to target bacteriophages, wherein the “bacteriophage has been demonstrated to deplete a population of beneficial bacterium” (instant claims 18, 26); and “engineered to comprise one or more mutations in one or more bacteriophage receptors” to confer resistance (instant claim 22), and wherein the “disease, disorder, or condition is inflammatory bowel disease (IBD) or irritable bowel syndrome, Crohn's disease, ulcerative colitis, or immunotherapy-related colitis” (instant claim 25), have not been explicitly disclosed by the cited prior art reference of Barrangou et al, as discussed above.
Stuer-Lauridsen et al (2008), while teaching bacteriophage resistant lactic acid bacteria (LAB, probiotics) for use in compositions such as starter culture for manufacturing food or feed products (see title, Abstract, [0029], and Summary of the Invention), wherein the LAB probiotic bacteria are suitable oral ingestion to subjects suffering from or susceptible to a microbiome-dysfunction-associated disease, disorder, or condition (see paragraphs [0081], for instance) for suppressing harmful microorganisms in the gastrointestinal (GI) tract, by enhancing the immune system or by contributing to the digestion of nutrients; and wherein the therapeutic LAB comprise a mutation in one or more receptors of the therapeutic bacteria for a target bacteriophage-receptor binding protein (a bacterial strain with pip, a chromosomal bacteriophage receptor gene, that has been inactivated via mutation; see paragraphs [0005]-[0006], [0038], for instance), which confers resistance to certain bacteriophages that infect Lactococcus strains, in particular. Thus, Stuer-Lauridsen et al demonstrate the fact that mutations in the gene for the receptor for bacteriophages that infect beneficial therapeutic bacteria can be used as a method to control the bacteriophages and thus provide better probiotic bacterial populations for ingestion and/or use in subjects in need thereof, such as subjects having GI dysfunctions caused by harmful microbes that are part of the gut microbiome of the subject (i.e. akin to probiotic therapy; see [0081], for instance).
Cornuault et al (2018) disclose bacteriophages infecting Faecalibacterium prausnitzii, the bacterial population which is known to be one of the most abundant bacterial species (belongs to Clostridiaceae; see Title, Abstract, and page 2, left column, for instance) of the human GI tract microbiota, and has been known in the prior art for its anti-inflammatory activity in gut; wherein “a low abundance of this species has been regularly reported in the gut microbiota of inflammatory bowel disease (IBD) patients” (see Background on page 1, for instance); wherein they disclose virulent temperate phages (belonging to Myoviridae family; see Table 1 on page 3, for instance) that have been linked to dysbiosis of intestinal microbiota, and “some of them are either more prevalent or more abundant in the fecal samples of IBD patients compared to healthy controls” (see page 2, left column, and “Results”, Table 1, and “Conclusion” on page 9, for instance); wherein “all the phages were classified among the Neck type 1, the largest clade of the Caudoviridae order…” (see Results, page 4, left column). Thus, Cornuault et al disclose and/or demonstrate temperate bacteriophages that infect the most abundant bacterial population F. prausnitzii and are directly linked to GI tract inflammatory disorders such as IBD (i.e. by depleting their abundance in GI tract of said patients with resulting increase in GI tract inflammation associated with IBD).
Thus, given the detailed disclosure and motivation provided by Stuer-Lauridsen et al and Cornuault et al as discussed in details above, it would have been obvious to an artisan of ordinary skill in the art to modify the engineered, therapeutic bacterial population disclosed by Barrangou et al (see detailed teachings above) such that they comprise one or more mutations in one or more bacteriophage receptors in order to avoid phage infection, i.e. resistant to respective bacteriophages thereof (see probiotic supplementation of such phages as disclosed by Stuer-Lauridsen et al, above), and such that CRISPER spacer is directed to a target sequence specific for such infecting bacteriophages that are linked to GI tract disorders such as IBD (as disclosed by Cornuault et al, above) in order to successfully enhance the populations of beneficial bacteria (such as non-pathogenic, commensals) in the GI tract of patients in need thereof, as already explicitly suggested by Cornuault et al as discussed above. Since, such mutational and engineering modifications of the beneficial bacterial populations (with reference to their specific infecting bacteriophages) have already been disclosed by the cited prior art references as discussed in details above, an artisan in the art would have been able to successfully modify them for their beneficial effects for use in patients (such as IBD patients) in need thereof. It is to be noted that instant claims (see claim 18, in particular) are not limited to any specific “therapeutic bacteria” or any particular “distinct target bacteriophage”, target sequences, or any particular “bacteriophage receptor” per se, and therefore, no criticality can be attached to current generic presentation of the claimed scope (see applicant’s disclosure in Figures 4-5, in particular), unless evidence/data presented on record to the contrary. The invention as claimed fails to distinguish itself over the combined teachings and/or suggestions from the cited prior art references as discussed above.
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).
Examiner’s Response to Applicant’s Arguments
Applicant's arguments filed 02/12/2026 (see REM, p. 2-3) have been fully considered but they are not persuasive for at least the following reason of record:
Regarding the 103(a) rejection of record applicants mainly argue the following:
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In response, first, it is noted that instant claims (see independent claim 18, in particular) are not limited to any specific “therapeutic bacteria” or any particular “distinct target bacteriophage” or any specific target nucleotide or spacer sequence(s) per se. Second, the instant disclosure of record does not specifically define the term “spacer” directed to, or in context of any specific “target bacteriophage” per se (see instant SPEC, [0029], [0034], and more specifically Example 3, para [0198]). Moreover, as noted above in the rejection of record, Barrangou et al already disclose the therapeutic bacteria, wherein each comprise a clustered regularly interspaced short palindromic repeats (CRISPR) spacer that targets the one or more target bacteriophages (engineering the CRISPR loci in the cell such that they comprise one or more CRISPR spacers complementary or homologous to sequences from the bacteriophage; see paragraphs [0129], [0305]-[0306], claims 23-27, Figs. 1-2, 11-12, for instance); wherein suitable therapeutic bacteria include probiotic, lactic acid bacteria such as Bifidobacterium species, Lactococcus species, and Lactobacillus species (see paragraphs [0059], [0377], for instance); and wherein the target bacteriophage (that infect the bacterial strains) may include bacteriophages from families such as myoviridae, podoviridae, siphoviridae, etc. (i.e. phage families of the order Caudovirales; see [0004], [0059], [0292], claims 7-8, for instance). Thus, given the combined disclosure in the cited prior art references of record, the invention as generically claimed would have been obvious and/or fully contemplated by an artisan of ordinary skill in the art, unless evidence/data provided on record to the contrary (which is currently lacking on record).
Applicants are also advised 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 by applicants on record is not commensurate in scope with the degree of protection sought by the claim (see instant claim 18, in particular).
Thus, the 103(a) rejection of record is properly made and maintained.
Conclusion
NO claims are currently allowed.
Pertinent Prior Art:
1. Tetz et al (2017; NPL previously made of record) - “Bacteriophages as potential new mammalian pathogens”, Scientific Reports, Published online on 1st August 2017, 7: 7043; DOI:10.1038/s41598-017-07278-6; total pages 1-9 (disclose and explicitly demonstrate the fact that bacteriophages act as potential pathogens as they affect intestinal permeability and thus translocation of gut bacterial triggering various pathological conditions associated with chronic inflammation in subjects; wherein they experimentally demonstrated that oral bacteriophage challenge in animal model was able to deplete beneficial bacteria in the gut including Faecalibacterium, Lactobacillus, etc., and caused an increase in diversity of harmful unclassified bacterial species that are linked to various GI disorders including IBD, Crohn’s disease, etc.; see Abstract, entire “Results”, pages 3-5, Figs. 3-4, for instance).
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 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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SATYENDRA K. SINGH
Primary Examiner
Art Unit 1657
/SATYENDRA K SINGH/Primary Examiner, Art Unit 1657
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