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 the Claims
Claims 1, 6, 9, 17, 32, 34, 36, 40, 44, 63, 80, 84, 87, 89, 91-96 are currently pending (claim set as filed on 8/10/2026). Claims 2-5, 7-8, 10-16, 18-31, 33, 35, 37-39, 41-43, 45-62, 64-79, 81-83, 85-86, 88, and 90 are cancelled. Claims 80, 84, 87, and 89 are withdrawn due to a restriction/election requirement. Claims 1, 6, 32, 34, 36, and 44 are amended. Claims 91-96 are new. Claims 1, 6, 9, 17, 32, 34, 36, 40, 44, 63, and 91-96 are under examination.
Priority
This application filed on 9/29/2023 claims benefit to a provisional application no. 63/428,708, filed on 11/29/2022. The claim to benefit is acknowledged and therefore, the effective filing date of the application is 11/29/2022.
Withdrawal of Rejections
Any rejections of record not particularly addressed are withdrawn in light of the amendments and/or applicant’s comments.
Claim Rejections - 35 USC § 112
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 94 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.
Regarding claim 94, the recitation of “retains at least 20% upon wet granulation” renders the claim indefinite as it is unclear as to what property is being retained upon completing such a process.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 1, 6, 32, 34, 40, 44, 63, and 91-96 are rejected under 35 U.S.C. 103 as being unpatentable over Lobacki (Patent No. US 11,351,205 B2 – date of patent 6/7/2022) and as evidenced by Vermont Agency of Agriculture (Vermont Agency of Agriculture, “Eye on E. coli: Understanding pathogens of concern for fruit and vegetable farms”, 2022 Jan 12, www.agriculture.vermont.gov/produce-program/eye-e-coli understanding-pathogens-concern-fruit-and-vegetable-farms, accessed 2026 Mar 27, pgs. 1-3).
Lobacki’s general disclosure relates to the administering of a pharmaceutical therapeutic microbial composition (see abstract) comprising Escherichia coli bacteria (see col. 37, ¶ 3) and sugars such as glucose (see col. 76, ¶ 3) in a lyophilized state (see col. 29, ¶ 4).
Regarding claim 1, Lobacki teaches a therapeutic composition comprising the bacteria Escherichia coli (see col. 37, ¶ 3) and prebiotics comprising glucose, fructose, sucrose, and a combination thereof (see col. 53, ¶ 5). As the prior art teaches the same sugars as the claim recites, they read on the stabilizing excipient limitation. Lobacki discloses the therapeutic composition can be freeze-dried (see col. 29, ¶ 4). Lobacki further discloses that the microbial active ingredient and the glucose carrier can be added to form a homogenous mixture (see col. 76, ¶ 3), which indicates a uniform composition wherein the ratio of ingredients are equal to each other, and that the active ingredient concentration in the composition is about 2-70% (see col. 50, ¶ 4). Thus the concentration of the glucose would also be at a range of 2-70%, which fully encompasses the claimed concentration of 7-50%.
Lobacki suggests the combination of the E.coli bacteria and the prebiotics, but one would not immediately envisage the combination as claimed.
However, it would be obvious to one of ordinary skill in the art to combine the E. coli bacteria
and stabilizing excipients together in the composition taught by Lobacki. Motivation to do so would be
because Lobacki teaches an E.coli bacteria in a composition and excipients of glucose, fructose, sucrose,
and a combination thereof in a composition. Hence, the ordinary artisan would find it obvious to
combine both the bacteria and excipients from Lobacki’s suggestion into one composition as Lobacki
teaches that the excipients are prebiotics that nutritionally supplement the bacteria in the microbial
composition (see col. 53, ¶ 4).
Regarding claim 6, Lobacki teaches a second excipient of caffeine (see col. 71, ¶ 2). Lobacki discloses caffeine as a component of the polymer coating of the encapsulated therapeutic microbial composition.
Regarding claim 32, Lobacki teaches the therapeutic composition exhibits a microbial concentration between at least 1 x 106 to 1 x 1014 CFU (see col. 26, ¶ 2), which fully encompasses the claimed concentration of at least 1 x 106.
Regarding claim 34, Lobacki teaches the therapeutic composition comprising the bacteria E.coli (see Lobacki col. 37, ¶ 3) and prebiotics comprising glucose, fructose, sucrose, and a combination thereof (see Lobacki col. 53, ¶ 5) in a lyophilized state (see Lobacki col. 29, ¶ 4). As evidenced by Vermont Agency of Agriculture, inherently E.coli bacteria can be stable for months at a temperature range of 45-121[Symbol font/0xB0]F or 7.2-49.4[Symbol font/0xB0]C (see Vermont Agency of Agriculture pg. 3, ¶ 4), which fully encompasses the claimed value of “about 23[Symbol font/0xB0]C”.
Regarding claim 40, Lobacki teaches that the therapeutic composition is stable when exposed to organic solvents such as ethanol and chloroform during lyophilization (see col. 29,¶ 4).
Regarding claim 44, Lobacki teaches that the therapeutic composition is embodied as a tablet (see col. 74, ¶ 2). Lobacki discloses that upon exposure to the organic solvent, the bacteria can lose 10-99.9999% of its viability (see col. 33, ¶ 2); it would be reasonable to interpret that the remaining viability is between 0.0001-90%, which encompasses at least 5%.
Regarding claim 63, Lobacki teaches that the therapeutic composition is stable when exposed to ionizing radiation as the microbes are prepared under irradiating conditions (see col. 40, ¶ 2).
Regarding claims 91-92, Lobacki teaches the therapeutic composition can be in the form of a tablet (see col. 74, ¶ 2) or powder (see col. 51, ¶ 3).
Regarding claim 93, Lobacki teaches the therapeutic composition can be pulverized (see col. 51, ¶ 3), which is a form of milling. Lobacki further discloses that the total cell count of the microbes in the composition ranges from 1 x 105 to 1 x 1015 CFU (see col. 44, ¶ 7), and that the number of viable cells after preparing a solid composition ranges from 1 x 105 to 1 x 1013 CFU (see col. 76, ¶ 3). This calculates to at least a 5% viability of the cells retained.
Regarding claim 94, Lobacki teaches the therapeutic composition can be in solid form and mixed with a wetting agent such as water to form a homogenous mixture (see col. 76, ¶ 3), which reads on wet granulation. As noted in the 112b above, it is unclear as to what property is being retained “at least 20%” upon such a process. For examination purposes, the homogenous mixing of the therapeutic composition to retain a 50/50 percentage of the active microbial ingredient and the carrier reads on the claim limitation.
Regarding claim 95, Lobacki teaches additional therapeutic agents can be spray-coated onto the therapeutic composition capsule (see col. 75, ¶ 5). Lobacki further discloses that the total cell count of the microbes in the composition ranges from 1 x 105 to 1 x 1015 CFU (see col. 44, ¶ 7), and that the number of viable cells after preparing a solid composition ranges from 1 x 105 to 1 x 1013 CFU (see col. 76, ¶ 3). This calculates to at least a 0.2% viability of the cells retained.
Regarding claim 96, Lobacki teaches the therapeutic composition can be in the form of an acid-resistant tablet (see col. 51, ¶ 1), which suggests stability of the composition upon exposure to acid in the gastrointestinal tract for instance.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Lobacki (Patent No. US 11,351,205 B2 – date of patent 6/7/2022) and further in view of von Maltzahn (US Patent No. US 10,314,853 B2 – date of patent 6/11/2019).
Lobacki’s general disclosure has been set forth above.
Regarding claim 9, Lobacki teaches a therapeutic composition that comprises a caffeine stabilizing excipient (see col. 71, ¶ 2).
Lobacki does not teach a stabilizing excipient of melibiose.
Von Maltzahn’s general disclosure relates to the use of pharmaceutical glycan therapeutics comprising melibiose to modulate and prevent harmful bacterial growth (see abstract, see col. 24, ¶ 4, and col. 21, ¶ 1).
Regarding claim 9, von Maltzahn teaches a glycan therapeutic composition (see abstract) comprising melibiose as a starting material for the polymerization reaction (see col. 24, ¶ 4).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add melibiose as taught in von Maltzahn to the therapeutic bacterial composition taught in Lobacki. Motivation to do so would be because von Maltzahn teaches that glycans such as melibiose can prevent the growth of harmful microbes (see von Maltzahn col. 21, ¶ 1). Lobacki discloses a need for healthy donated fecal samples that are free from pathogenic microbes (see Lobacki col. 33, ¶ 2-3 and col. 34, ¶ 1) for use in the therapeutic bacterial composition. The addition of melibiose to Lobacki’s composition would be considered advantageous as it could inhibit the growth of pathogenic microbes.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Lobacki (Patent No. US 11,351,205 B2 – date of patent 6/7/2022) and further in view of Kanthasamy (Pre-Grant Publication No. US 2019/0262298 A1– date of publication 8/29/2019).
Lobacki’s general disclosure has been set forth above.
Regarding claim 17, Lobacki teaches a therapeutic microbial composition comprising E.coli bacteria (see col. 37, ¶ 3).
Loback does not specify that the strain was E.coli Nissle 1917.
Kanthasamy’s general disclosure relates to an engineered probiotic E.coli Nissle 1917 strain (see [0008]) that is non-pathogenic (see [0049]) and used as a pharmaceutical agent (see [0005]).
Regarding claim 17, Kanthasamy teaches a pharmaceutical composition comprising an E.coli Nissle 1917 probiotic strain (see [0008]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the E.coli Nissle 1917 strain as taught in Kanthasamy within the therapeutic composition as taught in Lobacki. The ordinary artisan would have been motivated to do so because Nissle 1917 is known as a non-pathogenic probiotic strain of E.coli (see Kanthasamy [0049]). Since Lobacki is directed towards an ingestible microbial composition, substituting the E.coli strain to Nissle 1917 would be advantageous as it would be safe for subject consumption and the state of the art indicates its routine use.
Claim 36 is rejected under 35 U.S.C. 103 as being unpatentable over Lobacki (Patent No. US 11,351,205 B2 – date of patent 6/7/2022) in view of FDA (Food and Drug Administration, “Guideline for the Determination of Residual Moisture in Dried Biological Products”, 1990 Jan, pgs. 1-2).
Lobacki’s general disclosure has been set forth above.
Regarding claim 36, Lobacki teaches that the therapeutic composition is stable at low moisture after lyophilization (see col. 29, ¶ 4) and that it is also stable for at least one month (see col. 25, ¶ 4).
Lobacki does not specify that the humidity was at less than about 5%.
FDA’s general disclosure relates to guidelines for moisture content of biologicals post-lyophilization (see introduction and pg. 2, ¶ 3).
Regarding claim 36, FDA teaches a humidity of at less than about 5% (see pg. 2, ¶ 3). FDA discloses that biologicals after lyophilization usually have a moisture content between 1-5%.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the humidity percentage to about 5% as taught in FDA of the lyophilized composition as taught in Lobacki. The ordinary artisan would have been motivated to do so because FDA teaches that 1-5% is a common moisture content range for biologicals undergoing the lyophilization process (see FDA pg. 2, ¶ 3). Therefore, it would be reasonable to optimize the humidity content of the bacterial composition to be at 5% or less as this would offer a reasonable expectation of success for providing stability for the lyophilized composition disclosed in Lobacki.
Response to Arguments
Applicant's arguments filed on 8/10/2026 have been fully considered but they are not persuasive.
The applicant argues that it is not obvious as to why one of ordinary skill in the art would be motivated to combine the separate teachings of a solid composition, freeze-dried composition, E.coli, and glucose/fructose/sucrose excipients as disclosed in Lobacki together into one composition as claimed. They argue that there is no reason for why E.coli would be selected in particular, especially when the prior art discloses therapeutic compositions comprising “no viable” E.coli in paragraph [0204]), and thus there would also be no reason to select glucose/fructose/sucrose excipients as prebiotics in this case. Further the applicant argues that Lobacki does not disclose freeze-drying the bacteria and/or the excipients as claimed, but rather compositions instead.
The therapeutic composition does allow for non-viable E.coli bacteria in some embodiments but it also allows for viable E.coli flora in other embodiments of the therapeutic composition (see col. 39, ¶ 4 and col. 40, ¶ 1). Thus the bacteria are considered active and could be combined into one composition with the prebiotics of glucose/fructose/sucrose for nutritional support as described in the rejection above. One of ordinary skill in the art would be motivated to select E.coli as the bacteria in the composition as it is suggested embodiment in a relatively narrow list of potential suitable microorganisms (see col. 39, ¶ 4 and col. 40, ¶ 1). Furthermore, as the prior art teaches the lyophilization of the therapeutic bacterial composition which comprises the aforementioned bacteria and excipients as embodied, then the prior art also teaches the lyophilization of the specified bacteria and excipients as components of the composition as well.
The applicant argues that the skilled artisan would not have been motivated to arrive at the composition as claimed based off the multiple selections that it would have required using Lobacki’s disclosure. Thus they argue this requires hindsight knowledge.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
The applicant argues the claimed composition provides unexpected results that could not have been predicted by the teachings of Lobacki and in view of Vermont Agency of Agriculture. They argue that the claimed composition unexpectedly preserves high viability of bacteria even upon application of environmental stressors.
However, if the claimed composition does in fact comprise bacteria that have high viability despite these stressors that results in a composition that is markedly different from the one disclosed in the prior art, the applicant must provide statistically significant proof of such a claim. See MPEP 716.02.
As the rejections under Lobacki still stands, the rejections of subsequent dependent claims under Lobacki and von Maltzahn, Kanthasamy, and/or FDA still stand as well.
Conclusion
No claims are allowed.
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.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Emmalee R. Williams whose telephone number is (571)272-5472. The examiner can normally be reached Monday - Friday 7:30 am - 5:00 pm.
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, Sharmila Landau can be reached at (571) 272-0614. 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.
/EMMALEE R WILLIAMS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/ Supervisory Patent Examiner, Art Unit 1653
