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 .
Status of claims
Clams 72-82 as filed on 10/13/2023 are currently pending and under examination.
Claim Rejections - 35 USC § 112
Indefinite
Claim 74 remains 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 74 is rendered indefinite by recitation of Lactobacillus reuteri strain 100-23. The sole designation of strain by the internal designation creates ambiguity in the claims. For example, the strains disclosed in this application could be designated by some other arbitrary means, or the assignment of the strain names could be arbitrary changed to designate other strains. If either event occurs, one’s ability to determine the metes and bounds of the claims would be impaired. See In re Hammack, 427 F.2d 1378, 1382; 166 USPQ 204,208 (CCPA 1070). Amendment of the claims to refer to the deposit accession number of the claimed strain in culture collection with IDA status (ATCC, for example) would obviate this rejection.
Deposit requirement
Claim 74 remains 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.
Claim 74 requires one of ordinary skill in the art to have access to a specific microorganism that is a specific strain 100-23 belonging to the species of L.reuteri.
Because the microorganism is essential to the claimed invention, it must be obtainable by a repeatable method set forth in the specification or otherwise be readily available to the public. If the microorganism is not so obtainable or available, the requirements of 35 U.S.C. 112 may be satisfied by deposit of the microorganism. The specification does not disclose a repeatable process to obtain the microorganism and it is not clear from the specification or record that the microorganism is readily available to the public.
The rejection may be overcome by establishing that each microorganism identified is readily available to the public and will continue to be so for a period of 30 years or 5 years after the last request or for the effective life of the patent, whichever is longer, or by an acceptable deposit as set forth herein. See 37 CFR 1.801-1.809.
If the deposit is made under the terms of the Budapest Treaty, then an affidavit or declaration by applicants or a statement by an attorney of record over his/her signature and registration number, stating that the deposit has been made under the Budapest Treaty and that all restrictions imposed by the depositor on availability to the public of the deposited material will be irrevocably removed upon issuance of the patent would satisfy the deposit requirement. See 37 CFR 1.808.
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.
Claims 72-76 and 78-82 remain rejected under 35 U.S.C. 103 as being unpatentable over WO 2001/11334 (Lin et al), Schwab et al (“Sucrose utilization and impact of sucrose on glycosyltransferase expression in Lactobacillus reuteri”. Systematic and Applied Microbiology. 2007, 30, pages 433-443), US 2008/0241226 (Abeln et al) and US 10,660,857 (Prakash et al).
WO 2001/11334 (Lin et al) teaches a method of treating disorders caused by small intestinal bacterial overgrowth including depression in a subject in need thereof (see abstract; see page 19, lines 17-21) by administering to the subject a therapeutically effective amount of a therapeutic composition comprising a probiotic agent including Lactobacillus reuteri (page 20, lines 19-20, 30). The subject under treatment also has gastrointestinal disorders or IBS as result of bacterial overgrowth (page 19, lines 17-21). Although the cited document does not explicitly recognize that L. reuteri expresses glucosyltransferase (GFT), it is well known that probiotic bacteria L. reuteri expresses glucosyltransferase (GFT), for example: see the reference by Schwab et al (abstract). Schwab also acknowledges that GFT affect competitiveness of L. reuteri, particularly in presence of sucrose (last line of abstract).
Thus, the cited reference WO 2001/11334 (Lin et al) teaches treating depression by administering a therapeutic composition with of Lactobacillus reuteri. But it is silent about incorporation of additional components such as a microsphere and a water-soluble carbohydrate in the therapeutic composition with probiotic agent L. reuteri.
However, incorporation or use of a microsphere or microcapsule and a water-soluble carbohydrate in the therapeutic composition with probiotic agent L. reuteri is a common and routine practice.
For example: US 2008/0241226 (Abeln et al) teaches administration of probiotic dosage compositions including L. reuteri (par. 0106) that are provided in forms of capsules and/or with encapsulating substances (0130, 0131) and including bacterial growth promoting compounds that are water-soluble carbohydrates including maltose and sucrose derivates (par. 0125). The probiotic suitable dose is about 107 CFU - 1012 CFU (par. 0093). The probiotic-containing compositions are provided in a single and/or multiple doses (par. 0103).
US 10,660,857 (Prakash et al) teaches that encapsulation of probiotic bacteria L. reuteri supports cellular metabolism, proliferation and provide for bacterial function (col.11, lines 15-28), that the common size of therapeutic spherical microcapsules is in the range 1-999 µm (col.11, line 22), that maltose and sucrose are common ingredients for cryoprotection that ensure viability of probiotic bacteria L. reuteri (col. 14, line 19), that various strains belonging to the same species of L. reuteri including ATCC 23272 are known and available as therapeutically suitable probiotics (col. 10, lines 4-12).
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was made to modify a method for treating depression of the cited WO 2001/11334 (Lin et al) by adding to the main therapeutically active and effective ingredient L. reuteri of the cited method some additional components that are well known and used in the art including microspheres/capsules and water-soluble carbohydrates with a reasonable expectation of success in treating depression with probiotic agent L. reuteri because additional components enhance performance of main active ingredient L. reuteri by protecting bacterial cells from harsh environment and by providing lactogenic nutrients affecting competitiveness of probiotic L. reuteri against small intestinal bacterial overgrowth causing depression.
The use of various prior art known strains belonging to the same species of L. reuteri is considered to be the use of equivalents in the lack of evidence to the contrary.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Claims 72-82 remain rejected under 35 U.S.C. 103 as being unpatentable over WO 2001/11334 (Lin et al), Schwab et al (“Sucrose utilization and impact of sucrose on glycosyltransferase expression in Lactobacillus reuteri”. Systematic and Applied Microbiology. 2007, 30, pages 433-443), US 2008/0241226 (Abeln et al) and US 10,660,857 (Prakash et al) as applied to claims 72-76 and 78-82 above, and further in view of US 4,462,982 (Samejima et al).
The cited WO 2001/11334 (Lin et al), Schwab et al., US 2008/0241226 (Abeln et al) and US 10,660,857 (Prakash et al) as above.
The cited prior art clearly recognizes beneficial use of probiotics in with microcapsules/microspheres but is silent about the use of specific material such as dextran-crosslinked with epichlorohydrin as encapsulating material for therapeutically active ingredients.
However, US 4,462,982 (Samejima et al) teaches that polymer materials swellable in water including dextran-crosslinked with epichlorohydrin provide for effective acceleration of release of the microcapsule core active ingredient in the digestive tract of subjects under treatment (see abstract; see table 1, item 13; see col. 6, lines 15-18).
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was made to use dextran-crosslinked with epichlorohydrin as encapsulating material of microcapsules with therapeutically active ingredient L. reuteri in the method for treating depression by administration of probiotic L. reuteri with a reasonable expectation of success in protecting biological and therapeutically effective function of L. reuteri provided with microcapsules and for its effective release from the microcapsules in the digestive tract of subjects under treatment because polymer materials swellable in water such as dextran-crosslinked with epichlorohydrin provide for effective acceleration of release of the microcapsule core active ingredient in the digestive tract of subjects under treatment.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Response to Arguments
Applicant's arguments filed 10/13/2025 have been fully considered but they are not persuasive.
With regard to claim rejection under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, Applicants argue that term “strain 100-23” is not indefinite because it is not just a laboratory designation strain number but reference to “well characterized” rodent specific strain (response page 2).
This argument is not found persuasive because the scope of the claims is directed to a particular therapeutic agent or to a specific strain from the species of Lactobacillus reuteri. The reference to the particular strain as a therapeutic agent must be clear and definite as, for example: designation of strains by well-established collection of microorganisms under terms of Budapest Treaty (ATCC, NRRL, etc). However, the designation of the claimed strain as “100-23” could be altered depending on laboratory research or specific clinical applications. This fact is demonstrated by Applicants’’ exhibit A which is a refence by Tannock. For example: see table 1 which discloses several mutants or derivatives of strain “100-23” all having different designations. Thus, there is a question of uncertainty about which one of 6 strains disclosed in table 1 might be a therapeutic agent as intended for the instant claims.
With regard to claim rejection 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, (deposit requirement) Applicants argue that the claim-recited “strain 100-23” is “well-know and well-characterized” and that it was available to the public prior filing date of the instant application(response page 3).
This argument is not considered persuasive because applicants fail to provide name and address of company or agency which offers this strain for sale or for public use. A reference to genome portal would be at best an information about strain sequence but a possession of a real product. Thus, one of skill in the art cannot make and/or use the invention or cannot practice the claimed method for treating depression in the lack of a real product (claimed strain).
With regard to claim rejection under 35 U.S.C. 103 as being unpatentable over WO 2001/11334 (Lin et al), Schwab, US 2008/0241226 (Abeln et al) and US 10,660,857 (Prakash et al) Applicants’ main argument is that the primary reference by Lin does not teach or suggest a method of treating depression by administering Lactobacillus reuteri but solely a method for treating of small intestinal overgrowth by administering antibiotics (response page 4).
This argument is not found persuasive.
WO 2001/11334 (Lin et al) teaches a method of treating disorders that are caused by small intestinal bacterial overgrowth including depression (see abstract; see page 19, lines 17-21), where the treatment is directed to eradicating the bacterial overgrowth and wherein after the small intestinal bacterial overgrowth is eradicated there is an improvement in depression (see page 19, lines 17-21). In the preferred method the eradication of small intestinal bacterial overgrow employs a probiotic agent that is Lactobacillus reuteri (page 20, lines 19-20, 30). The fact, that example 3 discloses administration of antibiotic as argued, does not exclude the other preferred embodiment taught by the cited reference.
Further, the secondary references US 2008/0241226 (Abeln et al) and US 10,660,857 (Prakash et al) demonstrate that teach incorporation or use of a microsphere or microcapsule and a water-soluble carbohydrate in the therapeutic composition with probiotic agent L. reuteri is a common and routine practice.
Thus, the cited references are in the same field of endeavor and seek to solve the same problems as the instant application and claims, and one of skill in the art is free to select components available in the prior art, In re Winslow, 151 USPQ 48 (CCPA, 1966).
With regard to claims rejected under 35 U.S.C. 103 further in view of US 4,462,982 (Samejima et al) Applicants argue that there would not be a motivation to use a dextran-crosslinked with epichlorohydrin as encapsulating material of microcapsules with therapeutically active ingredient L. reuteri in the method for treating depression by administration of probiotic L. reuteri with a reasonable expectation of success because there is no evidence on record that microspheres are capable of accommodating L. reuteri biofilm attachment and growth (response pages 6-7).
This argument is not found particularly persuasive because the cited US 4,462,982 (Samejima et al) teaches that the polymer materials including dextran-crosslinked with epichlorohydrin are swellable in water and they provide for effective acceleration of release of the microcapsule core active ingredient in the digestive tract of subjects under treatment (see abstract; see table 1, item 13; see col. 6, lines 15-18). Thus, the cited refences clearly suggests the use of polymer materials including dextran-crosslinked with epichlorohydrin for delivery and for release of a therapeutic agent, that would be a probiotic in the case of treating depression by the method of Lin, to a site of therapeutic action, that is a gastrointestinal tract in the case of treating depression by the method of Lin by eradication of bacterial overgrowth causing depression.
Thus, the cited references are in the same field of endeavor and seek to solve the same problems as the instant application and claims, and one of skill in the art is free to select components available in the prior art, In re Winslow, 151 USPQ 48 (CCPA, 1966).
No claims are allowed.
Conclusion
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.
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Vera Afremova
February 10, 2026
/VERA AFREMOVA/ Primary Examiner, Art Unit 1653