DETAILED ACTION
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 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
Claims 1-5 are 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 Heyndrickxia coagulans strain CB85 specified in the instant application as Bacillus coagulans CB85 (DSM 33893) and Lactiplantibacillus plantarum strain CB102 specified in the instant application as Lactobacillus plantarum CB102 (DSM 33894) are 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 bacterial strains.
• 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 two specific strains of bacteria in the method of claim 1 and its dependent claims, 2-5. Therefor it is by definition, not possible to practice the method of claim 1 without access to the specified strains of bacteria H. coagulans CB85 and L. plantarum CB102. It would be effectively impossible to reisolate those 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 Heyndrickxia & Lactiplantibacillus until one with the same sequence is found by chance, since no sequence has been specified in this application this is also by definition impossible. This would be overcome by providing access to H. coagulans CB85 and L. plantarum CB102 via an acceptable deposit of viable culture, that is made available to the public.
• It is noted that Applicants have provided evidence of deposited biological material, however a search of the Deutsche Sammlung von Mikroorgaismen und Zellkulturen (DSMZ) catalogue for DSM 33893 & 33894 did not show evidence of H. coagulans CB85 and L. plantarum CB102 being available to the public under those catalogue numbers; to the contrary that search rendered zero results, for more information see search notes with the file name DSMZSearchNotes20JAN26.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. It is noted that such a statement is not present in the instant application.
Scope of Enablement
Claims 1-5 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the prevention of the following specific SARS-CoV-2 infection-associated disorders during a SARS-CoV-2 infection: lymphopenia, granulocyte deficiencies (abnormally low levels of granulocytes), lung inflammation and lung injury, as interpreted from the results section of the specification of the instant application. The specification does not reasonably provide enablement for the broad claim of preventing any infection-associated disorder during a SARS-CoV-2 infection nor the specific assertions of preventing immune escape, cytokine storm or multisystem inflammatory syndrome (MIS). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The breadth of claims 1-2 & 4-5 is broad, encompassing many different SARS-CoV-2 infection-associated disorders to include but not limited to group consisting of: lung inflammation, lung injury, lymphopenia, granulocyte abnormalities, immune escape, cytokine storm and MIS, of claim 3. The breadth of claims 1-2 & 4-5 would also include disorders such as, but not limited to, Long COVID/Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), thrombosis and cardiac complications.
The nature of the invention is a process of preventing all of these different SARS-CoV-2 infection-associated disorders with the administration of the novel composition of live H. coagulans CB85 and heat-killed L. plantarum CB102 to a subject in need thereof. The prior art teaches that many strains of H. coagulans are useful when administered as live bacteria (which includes spores) to prevent diarrhea during infection by enteritis causing Alphacoronavirus 1 strain IMI K105 (Kharkiv, Ukraine) (Farber et. al. column 30). It also teaches that H. coagulans TBC169 in combination with C. butyricum CGMCC 0313.1 is useful for the prevention and treatment of COVID-19 (Cui et. al. results section) The prior art further teaches that postbiotics of L. plantarum ProBio88 as well as the isolated protein of lactococcine G from L. plantarum can bind to SARS-CoV-2 and prevent infection in vitro and in silico respectively (Rather et. al. & Balmeh et. al.) The prior art does not specifically teach the specific combination of live H. coagulans CB85 and heat-killed L. plantarum CB102 nor its use for the previously recited SARS-CoV-2 infection-associated disorders.
An ordinary artisan in the field of clinical microbiology would have experience planning, executing, collecting relevant data, data analysis and presentation of relevant findings for/from experiments to determine the efficacy of probiotics, postbiotics, prebiotics or combinations thereof as treatments for specified conditions, in animal models or human patients. Determining efficacy of a given probiotic for any given SARS-CoV-2 infection-associated disorder is complex but routine in the art of clinical microbiology. Thus, the level of ordinary skill in the art of clinical microbiology is high, as an ordinary artisan in this art needs specialized experience in experimental design, microbiological techniques and procedures and complex data analysis. The predictability of using the specific combination of live H. coagulans CB85 and heat-killed L. plantarum CB102 to prevent the infection-associated disorders of SARS-CoV-2 infection is low since that specific combination could not be found in the prior art.
The amount of direction provided by inventor and existence of working examples: the specification shows that the combination of live H. coagulans CB85 and heat-killed L. plantarum CB102 lymphopenia, granulocyte deficiency, lung inflammation and lung injury in the experimental results on the mouse models of SARS-CoV-2 infection. The specification does not provide evidence of using the specific combination of live H. coagulans CB85 and heat-killed L. plantarum CB102 to prevent immune escape, cytokine storm, MIS, Long COVID/Post-Acute Sequelae of SARS-CoV-2 Infection (PASC), thrombosis or cardiac complications. While not exhaustive, the previous list would be reasonably encompassed by the breadth of the claims in the instant application.
The amount of experimentation required to use the invention based on the content of the disclosure would be unreasonable. This is because it would require a person of ordinary skill in the art to design execute and analyze animal model or human patient experiments to test each of the claimed but not enabled SARS-CoV-2 infection-associated disorders before being able to use the method described in instant application to prevent any of those disorders.
Discussion of the Closest Prior art
Searching the prior art did not yield any references that teach the use of a composition of live H. coagulans CB85 and heat-killed L. plantarum CB102 used to prevent SARS-CoV-2 infection-associated disorders.
The closest prior art is the following: Farber et. al US 11,446,338 B2, 20 Sep. 2022, hereafter “Farber”), Cui et. al. (“Application of Clostridium butyricum in Preparing Preparation for Treating Coronavirus Infection”, Chinese patent 112843096 A, 28 May 2021, hereafter “Cui”), Rather et. al. (“Potential Adjuvant Therapeutic Effect of Lactobacillus plantarum Probio-88 Postbiotics against SARS-COV-2”, 24 Sep. 2021, Vaccines, 1067(9), hereafter “Rather”) and Balmeh et. al. (“Manipulated Bio Antimicrobial peptides from Probiotic Bacteria as Proposed Drugs for COVID-19 Disease”, 12 Jan. 2021, Informatics in Medicine Unlocked 100515(23), hereafter “Balmeh
Farber teaches the administration of live Bacillus coagulans (hereafter Heyndrickxia coagulans or H. coagulans) for the purposes of treating or preventing diarrhea caused by Alphacoronavirus 1 strain IMI K105 (Kharkiv, Ukraine), but does not teach the inclusion of heat killed L. plantarum in its composition nor does it teach the specific coronavirus SARS-CoV-2.
Cui teaches the administration of C. butyricum and H. coagulans for the treatment of COVID-19, but does not teach the addition of heat killed L. plantarum.
Rather teaches the use of L. plantarum Probio-88 postbiotics (cell extracts) for inhibiting the growth of SARS-CoV-2 in vitro, but did not teach the combination of those postbiotics with H. coagulans.
Balmeh teaches that a single protein from L. plantarum (Lactococcine G) would be capable of binding to and inhibiting the replication of SARS-CoV-2 viral particles, in silico, but did not teach any combination with live probiotics of any kind. Rather, Cui, Farber and Balmeh do not teach the particular strains recited in the instant claims (CB85 and CB102)
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 1-5 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4 & 5 of U.S. Patent No. 12,090,182. Although the claims at issue are not identical, they are not patentably distinct from each other because the broadest reasonable interpretation of the claims in the instant application are encompassed by the claims of ‘182. Specifically, the independent claim 1 and its dependent claims 4 &5 of recite “A method for alleviating particulate matter-induced lung injury, comprising administering to a subject in need thereof a pharmaceutical composition including at least one heat-killed lactic acid bacterial strain and a probiotic microorganism”. ‘182 further recites lists of bacteria that can be used as the heat-killed bacteria and the probiotic microorganism, which includes the L. plantarum CB102 and H. coagulans CB85 of the instant application. The instant application claims the use of the same composition in “preventing SARS-CoV-2 infection associated disorders” (claim 1) to include lung injury (claim 3). Under the broadest reasonable interpretation, this does not actually require that the subject have a SARS-CoV-2 infection at the time of administration, and there for the group of eligible subjects would also include individuals with particulate matter-induced lung injury. Thus, rendering the claims patentably indistinct, since the same composition can be administered to the same subject group for the same purpose.
Conclusion
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/G.A.W./Examiner, Art Unit 1651
/MELENIE L GORDON/Supervisory Patent Examiner, Art Unit 1651