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 .
Claim Objections
Claims 11-12 & 14 are objected to because of the following informalities: reciting “the patient”, this lacks antecedent basis though it is clearly understood to mean the subject. For the purposes of examination claims 11-12 & 14 are construed as referring to the administration of the multistrain probiotic formulation to the subject. Appropriate correction is required.
Claim 27 is objected to because of the following informalities: reciting CRP, this abbreviation should be defined in parentheses next to the C-reactive protein of claim 26. It is understood as referring to the C-reactive protein of claim 26 and for the purposes of examination is construed as such. Appropriate correction is required.
Claim 30 is objected to because of the following informalities: reciting “BDNF” abbreviation is undefined in the claims, though it is understood to refer to brain derived neurotrophic factor and for the purposes of examination is construed as such. Appropriate correction is required.
Applicant is advised that should claim 15 be found allowable, claim 28 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Biological Deposit
Claim 2 is rejected under 35 U.S.C.§ 112, first paragraph, as containing subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
• It is apparent that Bacillus coagulans Unique IS-2 (MTCC 5260), Lactobacillus rhamnosus UBL R-5 8 (MT CC 5402), Bifldobacterium lactis UBBLa-70 (MT CC 5400), Lactobacillus plantarum U BLP-40 (MT CC 53 80), Bijfdobacterium breve UBBr-01 (MTCC 25081) and Bifdobacterium infantis UBBI-01 (MT CC 25124) is required to practice the claimed invention. As such the biological material must be readily available or obtainable by a repeatable method set forth in the specification, or otherwise readily available to the public. If it is not so obtainable or available, the requirements of 35 USC 112, first paragraph, may be satisfied by a deposit of the aforementioned strains of bacteria.
• The process disclosed in the specification does not appear to be repeatable, it is not clear that the invention will work with commonly available material and it is not apparent if the biological materials considered necessary to make and use the invention is both known and readily available to the public. Applicant claims the use of a specific strains of bacteria. Therefor it is by definition, not possible to practice the method of claim 2 without access to the specified strains of bacteria: Bacillus coagulans Unique IS-2 (MTCC 5260), Lactobacillus rhamnosus UBL R-58 (MTCC 5402), Bifidobacterium lactis UBBLa-70 (MTCC 5400), Lactobacillus plantarum U BLP-40 (MTCC 5380), Bifidobacterium breve UBBr-01 (MTCC 25081) and Bifidobacterium infantis UBBI-01 (MT CC 25124). It would be effectively impossible to reisolate that exact strains of bacteria from known sources of the same species, and would require an undue investment of time and resources for one skilled in the art to even attempt it. Since such an endeavor would require isolating and sequencing bacteria until isolates with the same sequences are found by chance. This would be a monumental and unnecessary effort that would be easily avoided by providing access to the above strains of bacteria via an acceptable deposit of viable culture, that is made available to the public.
• A search of the MTCC catalogue for the claimed deposit numbers did not show evidence of any of the claimed strains being available to the public under those catalogue numbers, nor did a search for the specific genera and species. For further details see MTCCSearchNotes09FEB26.pdf.
• If the deposit is made under the terms of the Budapest Treaty, then a statement, affidavit or declaration by Applicants, or by an attorney of record over his or her signature and registration number, or by someone in a position to corroborate the facts of the deposit, that the instant invention will be irrevocably and without restriction released to the public upon the issuance of a patent, would satisfy the deposit requirement made herein.
Indefiniteness
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.
Claim 29 is 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 29 recites “The method of claim 29, wherein…”, this language renders the claim indefinite because it is unclear which claim it actually depends on since a claim cannot depend on itself, and thus could depend on any other claim. For the purposes of examination claim 29 is construed as reciting: “The method of claim 28, wherein”.
Improper dependence
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.
Claim 29 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 29 recites “The method of claim 29, wherein…” this is not a proper dependent claim because claims cannot depend on themselves. For the purposes of examination claim 29 is construed as reciting: “The method of claim 28, wherein”. 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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-6, 10, &12-31 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Venkataraman et al. (Effect of Multi-strain Probiotic Formulation on Students Facing Examination Stress: a Double-Blind, Placebo-Controlled Study, Probiotics and Antimicrobial Proteins(13) 12-18, 29JUN20, hereafter “Venkataraman”).
Regarding claims 1-6, 12-13 & 16: The daily, oral administration of between 106 to 1012 CFUs per dose, once or twice a day, of a multi-probiotic formulation comprising: Bacillus coagulans (Unique IS-2 MTCC 5260), Lactobacillus rhamnosus (UBL R-58 MTCC 5402), Bifidobacterium lactis (UBBLa-70 MTCC 5400), Lactobacillus plantarum (UBLP-40 MTCC 5380), Bifidobacterium breve (UBBr-01 MTCC 25081) Bifidobacterium infantis (UBBI-01 MTCC 25124) and 100-500 mg of Glutamine; for the purpose of preventing, treating or ameliorating at least one symptom of Treatment-Resistant Depression (TRD), wherein TRD is induced by chronic stress or early-life stress and also comprises one or more of the following symptoms: irritability, mood swings, depressed mood, disturbed sleep, listlessness, cognitive changes, short term memory loss, anxiousness, restlessness, tension, and anhedonia . Also the probiotics are administered in a ratio of 2:2:2:2:1:1 as a food, supplement or pharmaceutically acceptable composition.
Venkataraman teaches the twice daily oral administration of the exact multi-probiotic formulation with the exact same strains in the same ratio and a dose of 2 or 1x109 CFUs per dose and 250 mg of glutamine, in the form of a pharmaceutically acceptable composition (capsule for oral administration), with the effect of decreasing score on the Perceived Stress Scale (PSS), Depression Anxiety Stress Scale (DASS) and the State-Trait Anxiety Inventory (STAI) questionnaire, as well as reductions to serum cortisol levels (abstract). Thus, the above claims are anticipated, since preventing a symptom of TRD does not require the subject to have TRD or even a manifested symptom of TRD.
Regarding claims 10, 14-15, & 17-31: wherein the multistrain probiotic formulation does or does not have the following effects:
10) does not affect metabolic activity or locomotor activity,
14) alleviates TRD symptoms by increasing gut eubiosis,
15 & 28-29) leads to an increase in goblet cells and improved crypt-to-villi ratio in the colon and a restoration of levels of tight junction (TJ) proteins,
17) a decrease of anhedonia,
18) alleviates TRD symptoms by modulating levels of tryptophan metabolites,
19) increasing levels of 5-HT,
20) restoring the elevated levels of L-tryptophan, L-kynurenine, kynurenic acid and 3-hydroxyanthranilic acid in the circulatory system,
21 & 22) reversing accumulation of neurotoxic metabolites associated with anxiety and depression: 3-hydroxyanthranilic acid,
23 & 24) decrease the levels of short chain fatty acids associated with anxiety and depression: acetate, propionate and or butyrate,
25) decreasing levels of proinflammatory cytokines,
26 & 27) reversing the elevated mRNA expression levels of TNA-alpha and C-reactive protein associated with anxiety and depression and dopamine levels in the hippocampus and or frontal cortex,
30) reverses the decrease in BDNF levels
31) reverses the decrease in Firmicutes to Bacteroidetes ratio in subjects showing symptoms of TRD.
Venkataraman teaches the administration of the exact same species of bacteria in a multistrain probiotic formulation, recited in claim 1, with 250 mg of glutamine to subjects with anxiety (as determined by the baseline STAI score of 48.58 +/- 8.25). The effects claimed in the instant application are inherent effects of administering this particular composition and thus must have been present in the subjects treated in the double-blind clinical trial of Venkataraman even if they were not explicitly observed during that trial.
Claim Rejections - 35 USC § 103
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 7-9 & 11 are rejected under 35 U.S.C. 103 as being unpatentable over Venkataraman as applied to claims 1-6, 10, &12-31 above, and further in view of Mousset et al. (Composition For The Treatment Of Emotional Disorders, WO 2021005310 A1, 14JAN21, hereafter “Mousset”).
Venkataraman teaches the exact composition recited in the method of claim 1 of the instant application, administered to subjects within the same subject group, for a period of 4 weeks.
Venkataraman does not explicitly teach the dosage period of 6 weeks or 6-8 weeks or that the multistrain probiotic formulation is administered as an adjunct to standard medical treatment for depression.
However, Mousset teaches the administration of a probiotic composition comprising glutamine, extract of curcuma and Lactobacillus rhamnosus (abstract) and one or more probiotics selected from preferably but not limited to, lactobacilli, bifidobacteria, bacillus, streptococci, enterococci, propionibacteria or saccaromycetes (additional ingredients section) for the treatment or prevention of anxiety disorders and/or mood disorders, in particular depression (abstract). Mousset also teaches the composition above being administered alongside standard medical treatments for depression including as an adjunct (Last five paragraphs of Subject and Administration Regime before the examples section). Mousset further teaches the administration of their multistrain probiotic formulation for the treatment or prevention of depression for “about 24 hours, about 2 days, about 5 days, about 10 days, about 15 days, about 30 days or 1 month, about 2months, about 4 months, about 6 months, or about 1 year”.
Regarding claims 7-9 & 11: The method of claim 1 wherein the subject receives 1 to 2 doses per day for 6 weeks or 6-8 weeks, and also wherein the multistrain probiotic formulation is administered as an adjunct to standard medical treatment for depression. It would be obvious to one of ordinary skill in the art to extend the treatment period of 4 weeks taught in Venkataraman to any of the administration durations taught in Mousset which includes “about 2 months” which would reasonably include anywhere from 6 to 8 weeks. One would have been motivated to do so since a longer dosage period requires the subject to purchase more of the multistrain probiotic composition while likely having even further benefits to the subject’s mental health. It would also be obvious to administer the multistrain probiotic formulation of Venkataraman as an adjunct to standard medical treatment as taught in Mousset with the expectation of success, and one would have been motivated to do so since this would expand the subject group taught in Venkataraman, which explicitly excluded individuals with diagnoses of psychological disorders, or that were on medication.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-10, &12-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10 & 16-17 of U.S. Patent Application No. 18/427,867. Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-8 & 10 of ‘867 recite the administration of the exact same composition to an overlapping subject group at the same ratio of bacterial strains for the same durations and dose and also in the same form of food product supplement or pharmaceutically acceptable composition as the instant application. Claims 16 & 17 of ‘867 recite the same inherent efficacies as claims 15 & 28 (increase in goblet cells and improved crypt to villi ratio) of the instant application as well as 25-27 (decrease in inflammatory cytokines, TNF-alpha and C- reactive protein) of the instant application.
Regarding claims 1-9, 12-13 & 16: The daily, oral administration of between 106 to 1012 CFUs per dose, once or twice a day, of a multi-probiotic formulation comprising: Bacillus coagulans (Unique IS-2 MTCC 5260), Lactobacillus rhamnosus (UBL R-58 MTCC 5402), Bifidobacterium lactis (UBBLa-70 MTCC 5400), Lactobacillus plantarum (UBLP-40 MTCC 5380), Bifidobacterium breve (UBBr-01 MTCC 25081) Bifidobacterium infantis (UBBI-01 MTCC 25124) and 100-500 mg of Glutamine; for the purpose of preventing, treating or ameliorating at least one symptom of Treatment-Resistant Depression (TRD), wherein TRD is induced by chronic stress or early-life stress and also comprises one or more of the following symptoms: irritability, mood swings, depressed mood, disturbed sleep, listlessness, cognitive changes, short term memory loss, anxiousness, restlessness, tension, and anhedonia . Also the probiotics are administered in a ratio of 2:2:2:2:1:1 as a food, supplement or pharmaceutically acceptable composition.
Claims 1-8 & 10 of ‘867 encompass the limitations of claims 1-9, 12-13 & 16 of the instant application because they recite administering the exact same composition to an overlapping group of subjects for the same durations at the same dose and ratios of probiotic strains, in the same form (food, supplement or pharmaceutically acceptable composition). The limitation of oral administration of claim 12 of the instant application is encompassed by the administration of the multistrain probiotic as a food product in claim 10 of ‘867, since food is consumed orally. The subject groups are considered overlapping because both applications recite a method of preventing a symptom of either TRD of instant application or Obsessive Compulsive Disorder (OCD) of ‘867. This does not limit the subject group in either case because preventing a symptom of a condition does not require that the subject have the condition or even be at risk of the condition, the subject would simply need to benefit from the prevention of one of those symptoms. Thus, further recitations of specific symptoms of either condition do not affect the scope of the subject group since any subject could benefit from the prevention of those symptoms.
Regarding claims 10, 14-15, & 17-31: wherein the multistrain probiotic formulation does or does not have the following effects:
10) does not affect metabolic activity or locomotor activity,
14) alleviates TRD symptoms by increasing gut eubiosis,
15 & 28-29) leads to an increase in goblet cells and improved crypt-to-villi ratio in the colon and a restoration of levels of tight junction (TJ) proteins,
17) a decrease of anhedonia,
18) alleviates TRD symptoms by modulating levels of tryptophan metabolites,
19) increasing levels of 5-HT,
20) restoring the elevated levels of L-tryptophan, L-kynurenine, kynurenic acid and 3-hydroxyanthranilic acid in the circulatory system,
21 & 22) reversing accumulation of neurotoxic metabolites associated with anxiety and depression: 3-hydroxyanthranilic acid,
23 & 24) decrease the levels of short chain fatty acids associated with anxiety and depression: acetate, propionate and or butyrate,
25) decreasing levels of proinflammatory cytokines,
26 & 27) reversing the elevated mRNA expression levels of TNA-alpha and C-reactive protein associated with anxiety and depression and dopamine levels in the hippocampus and or frontal cortex,
30) reverses the decrease in BDNF levels
31) reverses the decrease in Firmicutes to Bacteroidetes ratio in subjects showing symptoms of TRD.
Claims 1-8, 10 & 16-17 of ‘867 encompass the limitations of claims 10, 14-15, & 17-31 of the instant application because they recite administering the exact same composition to an overlapping group of subjects for the same durations at the same dose and ratios of probiotic strains, in the same form (food, supplement or pharmaceutically acceptable composition). The effects of the multistrain probiotic formulation recited in the instant application are inherent effects of administering the composition to a subject and thus are necessarily present in the methods of ‘867.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GREGORY WILLKEEN whose telephone number is (571)272-6184. The examiner can normally be reached 9:00-5:00 Mon-Fri.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie L. Gordon can be reached at (571) 272-1113. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/G.A.W./Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651