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
Claims 1-3, 5-12, and 26-27 are pending.
Response to Amendment
Applicant amended claims 1 and 27 and added new limitation “twice a week for three weeks”, and added the full names of acronyms Crh1, c-Fos, and Nr3c1.
Applicant amended the Incorporation by Reference paragraph in the specification to disclose the size of the sequence listing file in bytes.
The objection to the specification is withdrawn in view of the amendment.
The objection to claims 1 and 27 is withdrawn in view of the amendment.
The rejection of claims 1-3, 5-12 and 26-27 under 35 U.S.C. 103 is withdrawn in view of the amendment.
New Rejection Necessitated by the Amendment
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 1-3, 5-12 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Arias (Psychoneuroendocrinology 42 (2014): 207-217, of record in Office Correspondence mailed on 09/20/2024) in view of Cambejun (WO2021010118, published 01-2021, of record in IDS filed on 04/13/2023), Lenze (The American Journal of Geriatric Psychiatry 19.5 (2011): 482-490, of record in Office Correspondence mailed on 03/04/2025), Makino (Brain research 1048.1-2 (2005): 131-137), and Agrawal (US 2018/0243347 A1, published 08/30/2018), and as evidenced by Raff (Endocrinology 157.9 (2016): 3307-3308, of record in Office Correspondence mailed on 03/04/2025).
Regarding claim 1, Arias teaches stress-sensitive Germfree (GF) rats have higher serum corticosterone concentrations in response to the open-field stress (i.e. identifying a subject in need of improving one or more symptoms of behavioral deficit) (Abstract, Fig. 3). Arias teaches the GF rats have increased corticosterone levels compared to specific pathogen free (SPF) rats (i.e. detecting a level of corticosterone in the subject, wherein the subject has increased corticosterone levels compared to a healthy subject) (Fig. 3). Arias teaches consumption of the Lactobacillus rhamnosus JB-1 probiotic strain lowered the stress-induced corticosterone secretion and toned down the level of anxiety-like behavior in the elevated plus maze test (i.e. detecting the level of corticosterone in the subject after administration of the composition, wherein the subject has decreased corticosterone levels compared to the corticosterone levels before administration of the composition) (page 214 right column para. 1). Arias does not teach administering an effective amount of one or more Enterococcus bacteria.
However, Cambejun teaches germ-free mice exhibit enhanced corticosterone and adrenocorticotropic hormone in response to restraint stress than normal SPF mice ([0003]). Cambejun teaches administering a composition comprising bacteria belonging to the genus Enterococcus as an active ingredient and does not teach the presence of other bacteria (i.e., wherein the effective amount of the one or more Enterococcus bacteria is substantially free of bacteria other than the Enterococcus bacteria), and teaches the composition improves anxiety disorders and/or mood disorders ([0001]). Cambejun teaches the dose of the bacterium Enterococcus is 0.5x109 /kg body weight ([0045]). Applicant discloses an effective amount of Enterococcus bacteria is at least about 107 CFU (See specification [0012] and [0102]). Thus, the amount of composition taught by Cambejun falls within the limitation of “effective amount”. The limitations “thereby reducing corticosterone levels in the subject” and “wherein the one or more symptoms of behavioral deficit of the subject in need is improved after administering the one or more Enterococcus bacteria” do not require steps to be performed, and therefore, do not limit the method claimed. The whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited. Both Arias and Cambejun teach subject with anxiety have increased corticosterone levels. Thus, the subject population taught by Arias and Cambejun is the same subject population instantly claimed.
In addition, Lenze teaches treatment of anxiety disorder reduces the elevated cortisol levels in adults suffering from the disorder (title). Evidentiary reference Raff reports cortisol is the primary endogenous adrenal steroid in most mammals, including humans, whereas corticosterone is the primary adrenal corticosteroid in laboratory rodents (page 3307 left column second para.). Since Cambejun teaches the administration of the probiotic treated anxiety in the subject, one of ordinary skill in the art would expect a reduction of corticosterone levels in view of the teachings of Lenze and Arias.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method taught by Arias by administering an effective amount of a composition comprising bacteria belonging to the genus Enterococcus as an active ingredient to patients with anxiety as taught by Cambejun. One of ordinary skill in the art would be motivated to do so in order to improve the anxiety in the subject as taught by Cambejun. A skilled artisan would have a reasonable expectation of success in combining the teachings of these references to achieve the predictable outcome of improving one or more symptoms of behavioral deficit in a subject in need thereof.
Arias, Cambejun, and Lenze do not teach detecting a level of a product of Crh1 gene.
However, Makino teaches detecting the expression level of type 1 corticotropin-releasing hormone receptor mRNA which is increased during stress (Abstract). Applicant discloses Crh1 is Corticotropin-Releasing Hormone Receptor 1 gene (Remarks 11/03/2025 page 6).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Arias by detecting the mRNA levels of type 1 corticotropin-releasing hormone receptor, as suggested by Makino. One of ordinary skill in the art would be motivated to do so in order to detect biomarkers of stress and monitor the progress and effectiveness of the treatment. Since Arias teaches a desire to detect biomarkers of stress (corticosterone, CRF mRNA levels) and since Makino teaches type 1 corticotropin-releasing hormone receptor mRNA is a reliable stress indicator, there is a reasonable expectation of success. MPEP §2144.06(I) states that “[i]t is prima facie obvious to combine equivalents each of which is taught by the prior art to be useful for the same purpose.
Arias, Cambejun, Lenze, and Makino do not teach administering the bacteria twice a week for three weeks.
However, Agrawal teaches administering a probiotic twice a week ([0372]) over a period of time ranging from about two weeks to about four weeks ([0373]). Agrawal teaches administering the probiotic to treat inflammatory conditions that cause anxiety disorders ([0281]). Agrawal teaches the administration regimen depends on variety of factors such as severity of the symptoms and patient response ([0372]-[0373]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Arias by administering the probiotic twice a week and optimize the duration from about two weeks to about four weeks, as suggested by Agrawal. One of ordinary skill in the art would be motivated to do so in order to effectively treat the subject. Since Arias teaches administering a probiotic to tone down the level of anxiety-like behavior, Cambejun teaches administering a probiotic composition to improve anxiety disorders, and Agrawal teaches administering a probiotic to treat anxiety, there is a reasonable expectation of success.
Regarding claim 2, Arias teaches the behavioral deficit is anxiety (Abstract).
Regarding claim 3, Cambejun does not specifically teach Enterococcus is the sole active ingredient. However, one of ordinary skill in the art can be motivated to administer the bacterium Enterococcus faecalis as the sole active ingredient since Cambejun teaches this bacterium is an active ingredient (claim 4), thus suggesting no other active ingredients are needed for the composition to be effective.
Regarding claim 5, Cambejun teaches the composition comprises E. faecalis (claim 4).
Regarding claim 6, Cambejun teaches the active ingredient is E. faecalis (claim 4).
Regarding claim 7, Cambejun does not explicitly teach the composition is substantially free of bacteria other than the Enterococcus bacteria. However, Cambejun does not teach other bacteria are in the composition either. Cambejun teaches Enterococcus is an active ingredient and teaches the mice where fed AIN93-M (rodent feed) containing Enterococcus faecalis EC-12 strain ([0050]). One of ordinary skill in the art would be motivated to use a composition substantially free of bacteria other than Enterococcus faecalis since Cambejun does not teach other bacteria are needed for the composition to be effective. In addition, the addition of other bacteria might negatively affect the therapeutic effect of Enterococcus faecalis, thus rendering the composition less effective.
Regarding claim 8, Cambejun teaches the composition can be taken orally ([0038]).
Regarding claim 9, Arias teaches behavioral testing such as open field testing, sniffing, crawling, and following (Fig.1 and 2)
Regarding claim 10, Cambejun teaches the composition is a functional food classified as probiotic (paragraph [0041]).
Regarding claim 11, Cambejun teaches the composition is a health food ([0041]).
Regarding claim 12, Cambejun teaches the composition is used as a
pharmaceutical ([0022]).
Regarding claim 26, Cambejun teaches the dose of the bacterium Enterococcus is 0.5x109 /kg body weight (i.e., at least about 107 colony forming units) ([0045]).
Claim 27 is rejected under 35 U.S.C. 103 as being unpatentable over Arias (Psychoneuroendocrinology 42 (2014): 207-217, of record in Office Correspondence mailed on 09/20/2024) in view of Cambejun (WO2021010118, published 01-2021, of record in IDS filed on 04/13/2023), Lenze (The American Journal of Geriatric Psychiatry 19.5 (2011): 482-490, of record in Office Correspondence mailed on 03/04/2025), Makino (Brain research 1048.1-2 (2005): 131-137), Zimprich (Frontiers in behavioral neuroscience 8 (2014): 125, of record in IDS filed on 04/13/2023), Agrawal (US 2018/0243347 A1, published 08/30/2018), and as evidenced by Raff (Endocrinology 157.9 (2016): 3307-3308, of record in Office Correspondence mailed on 03/04/2025).
The teachings of Arias, Cambejun, Lenze, and Makino are discussed above and applied herein.
Arias, Cambejun, Lenze, and Makino do not teach administering to the subject in need a corticosterone synthesis inhibitor, thereby reducing corticosterone levels in the subject.
However, Zimprich teaches identifying stressed mice with symptoms of behavioral deficit (page 3 para. “stress protocol”, Figure 2), detecting the level of corticosterone (Figure 4) and administering a corticosterone synthesis inhibitor metyrapone to the mice under acute stress (Figure 5). Zimprich teaches the stress-induced hyperlocomotion is blocked by metyrapone (Abstract, Figure 5, page 125 left column first para.).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Arias by administering to the subject metyrapone, a corticosterone synthesis inhibitor, as suggested by Zimprich. One of ordinary skill in the art would be motivated to do so in order to block the stress-induced behavior. Since Arias and Zimprich teach a desire to treat behavioral deficit related to high level of corticosterone, there is a reasonable expectation of success. The limitation of “thereby reducing corticosterone levels in the subject” expresses the result of the active step positively recited and does not limit the claim.
Arias, Cambejun, Lenze, Makino, and Zimprich do not teach administering the bacteria twice a week for three weeks.
However, Agrawal teaches administering a probiotic twice a week ([0372]) over a period of time ranging from about two weeks to about four weeks ([0373]). Agrawal teaches administering the probiotic to treat inflammatory conditions that cause anxiety disorders ([0281]). Agrawal teaches the administration regimen depends on variety of factors such as severity of the symptoms and patient response ([0372]-[0373]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further modify the method taught by Arias by administering the probiotic twice a week and optimize the duration from about two weeks to about four weeks, as suggested by Agrawal. One of ordinary skill in the art would be motivated to do so in order to effectively treat the subject. Since Arias teaches administering a probiotic to tone down the level of anxiety-like behavior, Cambejun teaches administering a probiotic composition to improve anxiety disorders, and Agrawal teaches administering a probiotic to treat anxiety, there is a reasonable expectation of success.
Response to Arguments
Applicant's arguments filed 05/19/2026 have been fully considered but they are not persuasive.
Applicant argues the cited references do not teach administering to the subject in need, an effective amount of one or more Enterococcus bacteria twice a week for three weeks, and a person of skill in the art would not have been motivated to combine these references to achieve the recited methods.
In response to the argument, newly cited reference Agrawal teaches a dosing regimen for administering a probiotic to a subject. Agrawal teaches administering the probiotic twice a week for a duration of about two weeks to about four weeks, and teaches administering a probiotic to treat inflammatory conditions that cause anxiety disorders. One of ordinary skill in the art would be motivated to optimize the dosing regime in order to treat the subject depending on the severity of the symptoms and patient response, as taught by Agrawal. Since Arias, Cambejun, and Agrawal teach a desire to administer probiotics to a subject to treat anxiety, there is a motivation to combine the teachings of the prior art and have a reasonable expectation of success.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 MARY A CRUM whose telephone number is (571)272-1661. The examiner can normally be reached M-F 8:00-5:00 CT with alternate Fridays off.
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 W 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.
/MARY A CRUM/Examiner, Art Unit 1657
/THANE UNDERDAHL/Primary Examiner, Art Unit 1699
Prosecution Insights