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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/26/2026 has been entered.
DETAILED ACTION
Claims 1-20 are pending and under examination on their merits.
Priority
Applicant’s claimed invention is not fully supported by the U.S. provisional application 63/007,370. Applicant’s claimed invention is drawn to a method of preventing or treating SARS-CoV-2 infection by administering a probiotic composition comprising Streptococcus salivarius subsp. thermophilus and Lactobacillus. However, Applicant’s disclosure in the provisional application is limited to a probiotic composition with an intended use (“prophylaxis against human coronaviruses”).
The effective filing date of the claimed invention is the filing date of the PCT/CA2021/050477 (4/9/2021).
Response to Arguments
Applicant's arguments filed 1/26/2026 have been fully considered but they are not persuasive.
Applicant argues that the claims are entitled to the effective filing date of the U.S. provisional application 63/007,370 because “prophylaxis” implies “prevention” and “coronavirus” is a small genus with a limited number of species that includes SARS-CoV-2 (Arguments, paragraph 2 on page 8 and paragraph 2 on page 9).
In response, these arguments are unpersuasive, because the claimed invention is a method of either preventing or treating SARS-CoV-2. A composition with an intended use of prophylaxis (prevention) is not a method of treatment. Therefore, the claims are not entitled to the effective filing date of U.S. provisional application 63/007,370. In addition, the provisional application is the product specification for a single probiotic composition comprising three strains. None of the claims at present are limited to this probiotic composition.
Applicant argues against the enablement rejection under 35 U.S.C. 112(a) on the grounds that the process of achieving a target CFU concentration per gram involves a simple mathematical calculation and subsequent binding together of the probiotic material with other standard components to achieve a final probiotic composition with the target CFU concentration (Arguments, bottom paragraph on page 12). Applicant presents a formula for calculating the weight of probiotic raw material needed to achieve a target CFU (Arguments, formula at the top of page 13). Applicant submits that because probiotic bacteria are living organisms, they tend to die off over time due to various environmental factors, thus manufacturers of probiotic compositions commonly include an overage of CFUs of the desired bacteria in the final probiotic composition to ensure that the probiotic composition will possess the target CFU concentration until the end of its shelf life (Arguments, paragraph 2 on page 13).
In response, these arguments are unpersuasive to overcome the enablement rejection under 35 U.S.C. 112(a). With respect to the amount of probiotic in the composition, Applicant has not provided evidence to support the upper bound of the claimed concentration of probiotic, which is an order of magnitude higher than the amount in the prior art. Indeed, to achieve such desired concentrations, the person of ordinary skill in the art would have needed to include an even higher number of CFUs in the formulation (the overage in Applicant’s formula). There is no guidance provided within the specification on how to achieve such concentrations. Furthermore, the claimed method is drawn to either preventing or treating SARS-CoV-2 with a probiotic composition. The person of ordinary skill in the art would have faced undue experimentation to either prevent or treat SARS-CoV-2 with the claimed composition. Although probiotics in general have immunomodulatory activity, such activity is not commensurate in scope with either prevention or treatment. For example, Bottari et al. (International journal of food sciences and nutrition 72.3 (2021): 293-299; cited in the Non-Final Action mailed on 12/27/2024) suggests a potential role of probiotics in attenuating COVID-19 either through immunomodulatory actions on systemic inflammation or by direct interaction with the lungs, but cautions that not all probiotics are likely to be the same (left column paragraph 1 on page 5). Here, the working examples provided in the specification are insufficient to enable either prevention or treatment of SARS-CoV-2.
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.
Claims 1-20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains 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.
Per MPEP 2164.01(a), the following eight factors should be considered when determining whether the person of ordinary skill in the art would face undue experimentation to make and/or use the invention: (1) The nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. While it is not essential that every factor be examined in detail, those factors deemed most relevant should be considered.
Nature of the invention. The claims are drawn to a method of use for preventing or treating SARS-CoV-2 viral infection in a subject comprising providing an effective amount of a probiotic composition formulated to be ingested, comprising Streptococcus salivarius subsp. thermophilus and Lactobacillus. Claims 13-16 and 20 recite the effective amount of the composition in units of CFU/g of probiotic composition. The upper bound foreach of the ranges is in units of trillion CFUS/g (e.g. 1.3 trillion CFUs/g).
Breadth of the claims. The broadest reasonable interpretation of claim 1 is that the ingestion of the probiotic composition protects the subject from acquiring SARS-CoV-2 viral infection after exposure to the virus or treats the subject with SARS-CoV-2 viral infection. In other words, subjects taking the probiotic composition remain healthy or at least partially recover from SARS-CoV-2 viral infection. Therefore, the probiotic composition acts as an edible vaccine against SARS-CoV-2 infection or as an antiviral. There is no special definition provided in the specification for CFUs, although the term is discussed in the specification (bottom of page 4 through top of page 5). As such, the term CFUs is given its broadest reasonable interpretation as colony forming units (viable probiotic bacteria cells or spores).
State of the prior art and unpredictability. Ogel et al. (Biotech Studies 29.1 (2020): 18-28; cited in the Non-Final Action mailed on 12/27/2024) teaches that lactic acid bacteria are capable of enhancing both the innate and the adaptive immune responses in animal systems but the responses are generally strain and dose dependent (Abstract).
Infusino et al. (Nutrients 12.6 (2020): 1718; cited in the Non-Final Action mailed on 12/27/2024) teaches that while effective vaccines to prevent respiratory virus infections are available for influenza and adenoviruses, no effective therapies are available for other respiratory viruses such as those responsible for SARS-CoV-2 (paragraph spanning pages 5-6). Infusino suggests the use of probiotics represents a promising tool in the field of clinical research (paragraph 1 on page 6). Infusino concludes “Although solid evidence for probiotic utilization in the treatment of COVID-19 is still lacking, their complementary use may be proposed” (page 7, bottom paragraph).
Sundararaman et al. (Applied Microbiology and Biotechnology (2020) 104:8089–8104; cited in the Non-Final Action mailed on 12/27/2024) suggests that certain probiotics may be beneficial in the treatment of secondary complications of COVID-19 such as ventilator-associated pneumonia and gut dysbiosis but cautions that the immune stimulation and cytokine expression is strain specific and may vary according to the consortia of the probiotic bacteria (Conclusions on left column of page 8099).
Bottari et al. (International journal of food sciences and nutrition 72.3 (2021): 293-299; cited in the Non-Final Action mailed on 12/27/2024) suggests a potential role of probiotics in attenuating COVID-19 either through immunomodulatory actions on systemic inflammation or by direct interaction with the lungs, but cautions that not all probiotics are likely to be the same (left column paragraph 1 on page 5).
Antunes et al. (Food research international 136 (2020): 109577) teaches that different levels of evidence support the use of fermented foods, probiotics, and prebiotics to promote gut and lungs immunity (Abstract). However, Antunes cautions that although incorporating them into the diet may help to decrease gut inflammation and enhance mucosal immunity, they are not a promise of efficacy against COVID-19 (Abstract).
Mirashrafi et al. (Clinical nutrition ESPEN 46 (2021): 1-8) is a review article published just after the effective filing date of the claimed invention that summarizes the state of the art. Mirashrafi reviews the literature to assess evidence of antiviral activity of probiotics against COVID-19 (Abstract Methods). Mirashrafi concludes that some probiotic strains may be useful against viral infections but cautions that randomized trials are needed to confirm these findings (Abstract Conclusion).
With respect to the claimed probiotic composition, Tallei et al. (ID2021SID00097A; cited in the Non-Final Action mailed on 12/27/2024) teaches that recent research in South Korea showed that the probiotics Lactobacillus gasseri, L. rhamnosus and Streptococcus thermophilus isolated from fermented sea buckthorn berries were able to prevent the proliferation of SARS-CoV-2 (page 3, paragraph 1). However, the article cited by Tallei in the Korea Biomedical Review (2020, website; cited in the Non-Final Action mailed on 12/27/2024) suggests that the activity of the probiotic mixture is due to the presence of Lactobacillus gasseri (final paragraph on page 2), which is not part of the claimed invention. No actual data is provided by either Tallei or the Korea Biomedical Review.
With respect to the upper bound of the claimed concentration of the probiotic composition (1.3 trillion CFUs/g or 3 trillion CFUs/g in dependent claims 13-16 and 20), the state of the art does not teach such highly concentrated probiotic compositions. Rather, the state of the art teaches probiotic compositions on the order of 1011 CFUs/g, which is an order of magnitude less than the claimed concentration. For example, freeze-dried Streptococcus salivarius M18 has a concentration of 1011 CFU/g (M18 website, 2018; page 2, Definition of the ingredient, paragraph 2).
In summary, the state of the art just before the effective filing date of the claimed invention is highly speculative with respect to the efficacy of probiotics against SARS-CoV-2 and suggests a high degree of unpredictability in the art. The state of the art also does not teach Streptococcus salivarius probiotics with concentrations on the order of trillion CFUs/g.
Guidance in the specification and working examples. Example 1 of the specification (page 24 bottom paragraph) is a case study of reducing SARS-CoV-2 infection in human subjects. Applicant discloses that health care personnel and full time doctors and nurses in contact with those infected with SARS-CoV-2 were provided a probiotic composition comprising Streptococcus salivarius subsp. thermophilus, Lactobacillus delbrueckii subspecies bulgaricus, and Lactobacillus rhamnosus to reduce the risk of becoming infected with SARS-CoV-2. The participants took a dose of the probiotic 3 times daily for at least 30 days and at the 30 day mark there were no reports of SARS-CoV-2 within the study group, despite working in a high-risk environment with daily exposure to COVID-19 patients and articles. However, there is no corresponding control for the study group because there was no group of participants who did not take the probiotic composition. Furthermore, Applicant has not disclosed whether other forms of protection against viral infection were used by the participants (e.g. masks or gloves). Therefore, Applicant’s conclusion that the probiotic composition reduces the risk of becoming infected with SARS-CoV-2 is not supported by the data. In addition, the probiotic composition of Example 1 does not correspond to any of the probiotic compositions in the claimed invention because the probiotic compositions are either broader in scope (for example, the probiotic composition recited in claim 1 recites Lactobacillus rather than Lactobacillus delbrueckii subspecies bulgaricus and Lactobacillus rhamnosus) or differ in composition (claim 12 requires both Lactobacillus acidophilus and Lactococcus lactis, which are not included in the probiotic composition of Example 1).
Examples 2-3 of the specification (pages 25-26) pertain to treating COVID-19. Example 2 discloses a case study of a patient who ingested probiotics before and during a severe case of COVID-19. However, this example does not have a negative control since it presents a single patient. The example only serves as evidence that the probiotics do not have counter indications with COVID-19 treatments at the time. Example 3 describes administering the probiotic composition to COVID-19 inpatients and outpatients in Austria. The specification discloses that “Within two weeks 79.03% of the patients tested negative after two weeks. This is significant since the recovery rate for non-participants during the same period was 18.4%. During the time period of the study (April 13-27, 2020), the national recovery rate from COVID-19 in Bulgaria was 19.9% and the worldwide recovery rate was 31.1%.” However, no statistical analysis is performed between the experimental group and a control group to demonstrate a statistically significant difference.
The second cohort of the case study of Example 4 is a group of volunteers who have not been diagnosed with COVID-19 but have daily exposure risks (second to last paragraph on page 26). Applicant predicts that “The expected result is that the percentage of second cohort volunteers will have a lower rate of SARS-CoV-2 infection rate than those not taking the probiotic composition who are similarly situated” (paragraph 1 on page 27). However, no actual results are disclosed within the specification for the second cohort of Example 4. Furthermore, as discussed above with respect to Example 1, there is no corresponding control (volunteers who do not take the probiotic composition) for the experiment and no indication of other measures that might be used by the participants (e.g. masks or gloves).
With respect to the effective amount of the probiotic composition, Table 1 of the specification discloses viable lactic acid bacteria with concentrations of greater than 6.9 ×1012 CFU/g (Table 1 on page 13). However, no guidance is provided within the specification for how such a high concentration of CFUs/g probiotic composition are attained.
Amount of experimentation necessary. Given the lack of disclosure in the specification and unpredictability in the state of the art, the person of ordinary skill in the art would have faced undue experimentation to practice the invention as claimed. First, the person of ordinary skill in the art would have had to conduct clinical trials with all of the claimed probiotic compositions, including a representative number of Lactobacillus species and strains. The genus Lactobacillus contains over 260 distinct species (Zheng et al., Int. J. Syst. Evol. Microbiol. 2020;70:2782–2858; cited in the Non-Final Action mailed on 12/27/2024; Abstract). The person of ordinary skill in the art would have had to determine which, if any, of the species would have been capable of preventing or treating SARS-CoV-2 viral infection in combination with the remaining strains (Lactobacillus acidophilus, Lactobacillus delbrueckii, and Lactobacillus rhamnosus).
The upper bound for the effective amount of probiotic composition is extremely high: 1.3 trillion CFUs/g or 3 trillion CFUs/g (see dependent claims 13-16 and 20). The person of ordinary skill in the art would also have faced undue experimentation to concentrate so much of the probiotic within a gram of the composition given that no guidance was provided within the specification and the state of the art teaches Streptococcus salivarius probiotic concentrations an order of magnitude less than the claimed concentration.
Taking these factors into account, undue experimentation would be required by one of ordinary skill in the art to practice the claimed invention. Thus, the claims are not enabled by the disclosure.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CANDICE LEE SWIFT whose telephone number is (571)272-0177. The examiner can normally be reached M-F 8:00 AM-4:30 PM (Eastern).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached at (571)272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CANDICE LEE SWIFT/Examiner, Art Unit 1657
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657