Prosecution Insights
Last updated: April 19, 2026
Application No. 14/809,733

CRUSHED BACTERIAL BODY AND COMPOSITIONS THEREOF

Final Rejection §103§112
Filed
Jul 27, 2015
Examiner
MOSS, NATALIE M
Art Unit
1653
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Soma Gen-Ichiro
OA Round
12 (Final)
31%
Grant Probability
At Risk
13-14
OA Rounds
3y 3m
To Grant
50%
With Interview

Examiner Intelligence

Grants only 31% of cases
31%
Career Allow Rate
160 granted / 509 resolved
-28.6% vs TC avg
Strong +18% interview lift
Without
With
+18.4%
Interview Lift
resolved cases with interview
Typical timeline
3y 3m
Avg Prosecution
86 currently pending
Career history
595
Total Applications
across all art units

Statute-Specific Performance

§101
7.7%
-32.3% vs TC avg
§103
43.1%
+3.1% vs TC avg
§102
18.5%
-21.5% vs TC avg
§112
27.4%
-12.6% vs TC avg
Black line = Tech Center average estimate • Based on career data from 509 resolved cases

Office Action

§103 §112
Notice of Pre-AIA or AIA Status The present application is being examined under the pre-AIA first to invent provisions. DETAILED OFFICE ACTION This Office Action is in response to the papers filed on 10 June 2025. PRIORITY The Applicant claims priority to JP2011-132743 and PCT/JP2012/0651763. Certified translations have not neem provided. CLAIMS UNDER EXAMINATION Claims 1, 3-4, 7, 11, 13, 15 and 20-24 are pending and have been examined on their merits. WITHDRAWN REJECTIONS The previous rejections have been withdrawn due to claim amendment. NEW REJECTIONS New rejections have been necessitated by claim amendment. 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, 3-4, 7, 11, 13, 15 and 20-24 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 written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. Claims 1, 7 and 24 have been amended to recite the gram negative bacterium “is not a pathogen used for vaccine production”. Regarding the negative proviso: MPEP 2173.05(i) states any negative limitation or exclusionary proviso must have basis in the original disclosure. If alternative elements are positively recited in the specification, they may be explicitly excluded in the claims. The specification does not recite the use of any gram negative pathogens used for vaccine production. The terms “vaccine” or “vaccine production” do not occur in the specification. The recited limitation is not supported by the original disclosure, and are considered new matter All dependent claims are included in this rejection. Claims 3-4 are included in this rejection because they comprise the method recited in claim 1. Claims 1, 7 and 24 have been amended to recite “gram-negative bacterial cells containing LPS from a gram-negative bacterium”. The specification discloses all gram negative bacteria have LPS on the cell membrane ([0013]). As written, the claim is interpreted to mean the gram negative bacterial cells can contain LPS from a different gram-negative bacterium. The specification does not provide support for this limitation. This is new matter. All dependent claims are included in this rejection. Claims 3-4 are included in this rejection because they comprise the method recited in claim 1. Claims 20-21 recite a human subject. The specification does not provide support for a human subject. This is new matter. Claim 20 encompasses administering a feedstuff, pet food or veterinary drug to a human. The specification does not provide support for administering a pet food or veterinary drug to a human subject. This is new matter. Dependent claim 21 is included in this rejection because it depends on claim 20. An amendment to the claims or the addition of a new claim must be supported by the description of the invention in the application as filed. In re Wright, 866 F.2d 422, 9 USPQ2d 1649 (Fed. Cir. 1989). Applicant is required to cancel the new matter in the reply to this Office Action. 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. Claims 1, 3-4, 7, 11, 13, 15 and 20-24 are 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 1 has been amended to recite “administering the one or more brushed bacterial cells to a subject”. The claim recites crushing the gram-negative bacterial cells. There is a lack of antecedent basis for “the one or more” crushed bacterial cells. Appropriate correction is required. All dependent claims are included in this rejection. Claims 3-4 are included in this rejection because they comprise the method recited in claim 1. Claim 1 recites “the one or more cursed bacterial cells…”. It is unclear if the claim means “crushed”. The metes and bounds of the claim are unclear. Appropriate correction is required. All dependent claims are included in this rejection. Claims 3-4 are included in this rejection because they comprise the method recited in claim 1. Claims 1, 7 and 24 have been amended to recite “gram-negative bacterial cells containing LPS from a gram-negative bacterium”. The specification discloses all gram negative bacteria have LPS on the cell membrane ([0013]). It is unclear if the claim means the gram negative bacteria cells can contain LPS from different gram negative bacterium. The metes and bounds of the claims are unclear. Appropriate correction is required. All dependent claims are included in this rejection. Claims 3-4 are included in this rejection because they comprises the method recited in claim 1. In the interest of compact prosecution, the claims have been rejected under 35 USC 112a. Regarding claim 3: The method requires the method of claim 1. Claim 1 has been amended to require administration to a subject. Claim 3 recites the method of claim 1 is “followed by making the composition”. The claim language is unclear because claim 3 would require making the composition after it has been administered. The metes and bounds of the claim are unclear. Appropriate correction is required. Regarding claim 4: The method requires the method of claim 1. Claim 1 has been amended to require administration to a subject. Claim 4 recites the method of claim 1 is “followed by making the composition”. The claim language is unclear because claim 4 would require making the composition after it has been administered. The metes and bounds of the claim are unclear. Appropriate correction is required. The following is a quotation of 35 U.S.C. 112(d): (d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph: Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers. Claim 21 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 21 recites a the subject is a human or animal. The base claim (claim 20) recites a human. An animal subject does not further limit a human subject. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. Claim Rejections - 35 USC § 103 The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. Claims 1, 3-4, 20-21 and 23 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lanzilli et al. (previously cited; In Vitro Effects of An Immunostimulating Bacterial Lysate On Human Lymphocyte Function. International Journal of Immunopathology and Pharmacology. Vol. 18, no. 2, 245-254) in view of Sedelmeier et al. (previously cited; Biological activity of bacterial cell-wall components: immunogenicity of the bacterial extract OM-89. Immunopharmacology 29 (1995) 29-36), Groh et al. (previously cited; Effect of Heat on the Sterilization of Artificially Contaminated Water. J Travel Med 1998; 3:11-13), Invitrogen (previously cited; Cell Culture Basics. Page 1-62. 2010) and Lane et al. (previously cited; Characterization of the Cell Wall and Cell Wall Proteins of Chromatium vinosum. Journal of Bacteriology, Mar. 1980, pages1386-1398). Lanzilli teaches an oral immunostimulating vaccine (MLBL) consisting of bacterial standardized lysates obtained by mechanical lysis of different strains of Gram-positive and Gram-negative bacteria (Abstract). As evidenced by the PG Pub of the specification, gram-negative bacteria have lipopolysaccharides (LPS) on the membrane ([0013]).The art teaches it is a sublingual containing a mechanical lysate (obtained through sonication) of strains of bacteria (6 x 109 bacteria for each strain) selected among those most frequently implicated in acute and chronic infections of the respiratory tract (page 246, left column, third paragraph). Lanzilli teaches inactivated bacteria are advantageous for mucosal immunization (same cited section). Lanzilli teaches the following method of preparation: the bacteria were resuspended at the concentration of 1 x 1011 CFU/ml. The bacterial suspension was heat-inactivated, adjusted at pH 7.0, submitted to two homogenisation cycles at 630 bar by using an APV homogenisator and lyophilized (see page 246, right column, first paragraph). Homogenization is interpreted to read on crushing. A pressure of 630 is equal to 9137.88 psi (to convert BAR to PSI, multiply the pressure value in BAR by 14.5038). Because the APB homogenizer produces a high-pressure that reads on the claim, it is interpreted to be ahigh-pressure crusher. Lanzilli does not teach removal of any components of the lysate. Lanzilli teaches the MLBL may be lyophilized. Examiner notes claim 1 recites the transitional phrase “consisting essentially of”. This is open claim language that permits additional steps to be performed. Therefore claim 1 does not exclude lyophilization. The art teaches MLBL is a sublingual for oral administration. The art teaches vaccines are administered to improve immune response in subjects (see page 245, last sentence of left column bridging first 4 lines of right column). While Lanzilli teaches gram negative cells, the art does not teach the use of E. coli as recited in claim 1. While Lanzilli teaches “heat inactivation” the art is silent regarding the temperature at which heat inactivation occurs. While the art teaches the use of a bacterial cell suspension, the art does not explicitly teach culturing. Lanzilli does not teach cooling, or crushing during cooling. While Lanzilli teaches homogenization (hence, crushing), the art does not teach crushing 90% or more of cells. The art does not explicitly teach administration the composition to a subject. Sedelmeier et al. teach a bacterial extract prepared from 18 selected E. coli strains (a gram negative bacteria) has been shown to protect against bacterial infections in mice (page 29, left column, first paragraph). Therefore the art teaches administration to a subject. The composition is able to induce an immune response in mice(see page 33, right column, last paragraph bridging first paragraph of page 34). Because E. coli reads on claim 1, it is not interpreted to be a pathogen. It is well known in the art that water boils at 100 degrees Celsius. Groh teaches boiling (heating at 100 degrees Celsius) for 10 minutes is effective protocol for killing a gram negative bacteria (page 12, right column, “Heat Killing of Bacteria”). Invitrogen teaches cell culture is in large scale manufacturing of biological compounds (e.g., vaccines, therapeutic proteins). The major advantage of using cell culture is the consistency and reproducibility of results that can be obtained from using a batch of clonal cells. See page 3, last paragraph. Lane teaches the outer membrane of gram negative bacteria comprises lipopolysaccharides (page 1386, left column, first paragraph). Lane teaches a method of isolating the cell wall of C. vinosum (a gram negative bacteria; hence, an immunostimulatory composition). The art teaches the use of a "frozen cell paste” comprising frozen cells (page 1387, left column, “Membrane isolation” section”). The frozen cells are ruptured by a single pass through a French pressure cell at 4° Celsius (hence, lower than 20° Celsius) (same cited section). It would have been obvious to try using E. coli gram negative bacteria in the method taught by Lanzilli. One would have been motivated to do so since Lanzilli teaches a method of making a bacteria extract and Sedelmeier teaches E. coli can be used to make bacteria extract. One would have had a reasonable expectation of success since Lanzilli teaches gram negative bacteria can be used in the disclosed method. One would have expected similar results since both references bacteria extracts used to provide an immune response. It would have been obvious to the person of ordinary skill in the art at the time of the invention to heat inactivate gram negative bacteria at 100° Celsius. One would have been motivated to do so since Lanzilli which teaches heat-inactivating gram negative bacteria cells and Groh teaches gram negative cells can be heat inactivated at 100° Celsius. KSR Rationale A indicates that it is scientifically rational to combine prior art elements according to known methods to yield predictable results, when all of the claimed elements were known in the prior art and one skilled in the art could have combined the element as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable. One would have had a reasonable expectation of success since Groh teaches cells can be heat inactivated at this temperature. One would have expected similar results since both reference disclose heat inactivation of gram negative cells. Lanzilli teaches the use of 8 bacterial strains at a concentration of 6 x 109 bacteria for each strain. It is Examiner’s position the cells used by Lanzilli have necessarily been cultured to provide the claimed number of cells. Even arguendo they are not, it would have been obvious to culture cells. Lanzilli teaches 6 x 109 bacteria cells for each strain are used in the disclosed method. One would culture the gram negative bacteria cells used to prepare the composition taught by Lanzilli to obtain cells for obtain a batch of cells. Invitrogen teaches cell culture is also used in drug screening and development, and large scale manufacturing of biological compounds (e.g., vaccines, therapeutic proteins). Therefore one would culture cells to obtain the desired amount of cells. One would have had a reasonable expectation of success since Invitrogen teaches cells can be cultured. One would have expected similar results since Lanzilli and Invitrogen are directed to cell cultures. It would have been obvious to combine the teachings of Lanzilli and Lane by cooling the cited cells since Lane teaches a method of preparing an immunostimulatory composition that comprises crushing cells at 4° Celsius (hence, lower than 20° Celsius). The person of ordinary skill in the art would have been motivated to do so because KSR Rationale A indicates it is scientifically rational to combine prior art elements according to known methods to yield predictable results. In the instant case, one would have been motivated to do so since Lane teaches crushing cold cells to prepare an immunostimulatory composition. One would have had a reasonable expectation of success since Lane teaches cells can be crushed 4° Celsius. One would have expected similar results since both references are directed to compositions comprising immunostimulatory components obtained from crushing cultured gram negative cells. It would have been obvious to try to crush all of the bacterial cells (hence, more than 90%). Lanzilli teaches homogenization, which is defined as a process of reducing a substance to small particles (Britannica dictionary). Therefore the skilled artisan would want to crush as many cells as possible using the mechanical means disclosed by Lanzilli. Claim 1 recites the crushed bacterial cells include LPSs having molecular weights of 20,000 or less as active ingredients, and the crushed bacterial cells contain all components of the bacterial cell after heating. Because each of the claimed steps is rendered obvious, an extract prepared using E. coli in Lanzilli’s method would be expected to meet the limitations recited in claim 1. It would have been obvious to administer to a subject. One would have been motivated to do so to improve the immune response in a subject, as taught by Lanzilli. One would have had a reasonable expectation of success since Lanzilli teaches the vaccine is an oral formulation for sublingual administration. The preamble of the claim recites “the method consisting essentially of”. Because the specification does not clearly indicate what the basic and novel characteristics actually are, the art is interpreted to meet the claim limitation. See MPEP 2113.03 III. Therefore claim 1 is rendered obvious as claimed. Regarding independent claim 3: The claims require the method of claim 1. Lanzilli teaches a vaccine (supra). A vaccine is a pharmaceutical. Therefore the method of claim 3 is included in this rejection. Claim 4 recites a pharmaceutical for plants. The phrase “for plants” is an intended use and does not impart any structural limitations on a pharmaceutical. The method of claim 1 is rendered obvious. Therefore the method of making fertilizer, a compost or a pharmaceutical for plants as recited in claim 4 is rendered obvious. Therefore claim 4 is included in this rejection as claimed. It would have been obvious to treat a human. One would have been motivated to do so since Lanzilli teaches the composition activates an immune response in human cells (see first paragraph of Discussion on page 249). The composition taught by Lanzilli is a pharmaceutical. Therefore claim 20 is rendered obvious. Sedelmeier treats a mouse (animal). Therefore claim 21 is rendered obvious. Sedelmeier treats a mouse. Therefore in vivo administration as recited in claim 23 is rendered obvious Therefore Applicant’s Invention is rendered obvious as claimed. Claims 7, 11 and 13 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lanzilli et al. in view of Groh et al., Invitrogen, Lane et al. and in view of Thermo Electron Corporation (French Press Operation Manual. 2007. pages 1-62). Regarding independent claim 7: The teachings of Lanzilli as set forth above are reiterated. Lanzilli teaches “heat inactivation”, but is silent regarding the temperature. Lanzilli does explicitly teach that they have been cultured. The art does not teach cooling, or crushing during cooling. The art does not teach crushing 90% or more of cells. The art does not teach a PSI above 10,000. The teachings of Groh, Invitrogen and Lane as set forth above are reiterated. Thermo Electron Corporation teaches a French pressure cell is a dispersion unit for disintegrating cells, organisms and biological particles (see page 2, first paragraph). The art teaches pressures of 20,000 psi and 40,000 psi can be achieved (see page 5, section 16). It would have been obvious to the person of ordinary skill in the art at the time of the invention was made to heat inactivate gram negative bacteria at 100° Celsius. One would have been motivated to do so since Lanzilli teaches heat-inactivating gram negative bacteria cells and Groh teaches gram negative cells can be heat inactivated at 100° Celsius. One would have had a reasonable expectation of success since Groh teaches cells can be heat inactivated at this temperature. One would have expected similar results since both reference disclose heat inactivation of gram negative cells. As set forth above, Lanzilli teaches the use of 8 bacterial strains at a concentration of 6 x 109 bacteria for each strain. It is Examiner’s position the cells used by Lanzilli have necessarily been cultured to provide the claimed number of cells. Even arguendo they are not, it would have been obvious to culture cells. Lanzilli teaches 6 x 109 bacteria cells for each strain are used in the disclosed method. One would culture the gram negative bacteria cells used to prepare the composition taught by Lanzilli to obtain cells for obtain a batch of cells. Invitrogen teaches cell culture is also used in drug screening and development, and large scale manufacturing of biological compounds (e.g., vaccines, therapeutic proteins). Lanzilli teaches MLBL is a vaccine. Therefore one would culture cells to obtain the desired amount of cells. One would have had a reasonable expectation of success since Invitrogen teaches cells can be cultured. One would have expected similar results since Lanzilli and Invitrogen are directed to cell cultures. It would have been obvious to combine the teachings of Lanzilli and Lane by cooling the cited cells since Lane teaches a method of preparing an immunostimulatory composition that comprises crushing cells at 4° Celsius (hence, lower than 20° Celsius). In the instant case, one would have been motivated to do so since Lane teaches crushing cold cells to prepare an immunostimulatory composition. One would have had a reasonable expectation of success since Lane teaches cells can be crushed 4° Celsius. One would have expected similar results since both references are directed to compositions comprising immunostimulatory components obtained from crushing cultured gram negative cells. It would have been obvious to try to crush all of the bacterial cells (hence, more than 90%). Lanzilli teaches homogenization, which is defined as a process of reducing a substance to small particles. Therefore the skilled artisan would want to crush as many cells as possible using the mechanical means disclosed by Lanzilli. It would have been obvious to try using 10,000 psi in the method taught by Lanzilli. One would have been motivated to do so since Lanzilli teaches the use of a device to homogenize cells and Thermo teaches homogenizers with pressures of 20,000 can be used to homogenize cells. One would do so to produce the desired amount of cell disintegration. One would have had a reasonable expectation of success since Thermo Electron Corporation teaches pressures of 20,000 psi can be applied to cells. One would have expected similar results since both references are directed to cell homogenization. Because the art teaches crushed bacterial cells, they would be expected to activate innate immunity in a subject when administered. Claim 7 recites the crushed bacterial cell includes LPSs having molecular weights of 20,000 or less as active ingredients, and the crushed bacterial cell contains all components of the bacterial cell after heating. Because each of the claimed steps is rendered obvious, an extract prepared using E. coli in Lanzilli’s method would be expected to meet the limitations recited in claim 7. It would have been obvious to perform only the steps recited in claim 7. Lanzilli does not teach removal of any components of the lysate. While Lanzilli teaches lyophilization, the skilled artisan would exclude this step for a preparation that is not being stored. A method that does not comprise lyophilization would read on the consisting of language recited in claim 7. Therefore claim 7 is rendered obvious as claimed. A PSI above 15,000 is rendered obvious on the grounds set forth above. Therefore claim 11 is included in this rejection. It would have been obvious to crush more than 95% of the bacterial cells since Lanzilli teaches the composition is prepared by homogenizing cells. The skilled artisan would want to crush as many cells as possible using the mechanical means disclosed by Hashimoto. Therefore claim 13 is rendered obvious. Regarding independent claim 24: The teachings of the prior art are reiterated. It would have been obvious to the person of ordinary skill in the art at the time of the invention was made to heat inactivate gram negative bacteria at 100° Celsius. One would have been motivated to do so since Lanzilli which teaches heat-inactivating gram negative bacteria cells and Groh teaches gram negative cells can be heat inactivated at 100 degrees Celsius. KSR Rationale A indicates that it is scientifically rational to combine prior art elements according to known methods to yield predictable results, when all of the claimed elements were known in the prior art and one skilled in the art could have combined the element as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable. One would have had a reasonable expectation of success since Groh teaches cells can be heat inactivated at this temperature. One would have expected similar results since both reference disclose heat inactivation of gram negative cells. As set forth above, Lanzilli teaches the use of 8 bacterial strains at a concentration of 6 x 109 bacteria for each strain. It is Examiner’s position the cells used by Lanzilli have necessarily been cultured to provide the claimed number of cells. Even arguendo they are not, it would have been obvious to culture cells. Lanzilli teaches 6 x 109 bacteria cells for each strain are used in the disclosed method. One would culture the gram negative bacteria cells used to prepare the composition taught by Lanzilli to obtain cells for obtain a batch of cells. Invitrogen teaches cell culture is also used in drug screening and development, and large scale manufacturing of biological compounds (e.g., vaccines, therapeutic proteins). Lanzilli teaches MLBL is a vaccine. Therefore one would culture cells to obtain the desired amount of cells. One would have had a reasonable expectation of success since Invitrogen teaches cells can be cultured. One would have expected similar results since Lanzilli and Invitrogen are directed to cell cultures. It would have been obvious to combine the teachings of Lanzilli and Lane by cooling the cells since Lane teaches a method of preparing an immunostimulatory composition that comprises crushing cells at 4° Celsius (hence, lower than 20° Celsius). The person of ordinary skill in the art would have been motivated to do so because KSR Rationale A indicates it is scientifically rational to combine prior art elements according to known methods to yield predictable results. In the instant case, one would have been motivated to do so since Lane teaches crushing cold cells to prepare an immunostimulatory composition. One would have had a reasonable expectation of success since Lane teaches cells can be crushed 4° Celsius. One would have expected similar results since both references are directed to compositions comprising immunostimulatory components obtained from crushing cultured gram negative cells. It would have been obvious to try to crush all of the bacterial cells (hence, more than 90%). Lanzilli homogenization, which is defined as a process of reducing a substance to small particles (Britannica dictionary). Therefore the skilled artisan would want to crush as many cells as possible using the mechanical means disclosed by Lanzilli. Claim 24 recites the crushed bacterial cell includes LPSs having molecular weights of 20,000 or less as active ingredients, and the crushed bacterial cell contains all components of the bacterial cell after heating. Because each of the claimed steps is rendered obvious, an extract prepared using E. coli in Lanzilli’s method would be expected to meet the limitations recited in claim 24. It would have been obvious to use 20,000 psi to crush cells. One would have been motivated to do so since Lanzilli teaches the use of a device to homogenize cells and Thermo teaches homogenizers with pressures of 20,000 can be used to homogenize cells. One would do so to produce the desired amount of cell disintegration. One would have had a reasonable expectation of success since Thermo Electron Corporation teaches pressures of 20,000 psi can be applied to cells. One would have expected similar results since both references are directed to cell homogenization. The claim does not recite a step of administering to a subject. Because the art teaches crushed bacterial cells, they would be expected to activate innate immunity in a subject when administered. It would have been obvious to perform only the steps recited in claim 24. Lanzilli does not teach removal of any components of the lysate. While Lanzilli teaches lyophilization, the skilled artisan would exclude this step for a preparation that is not being stored. A method that does not comprise lyophilization would read on the consisting of language recited in claim Therefore claim 24 is rendered obvious as claimed. Therefore Applicant’s Invention is rendered obvious as claimed. Claim 15 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lanzilli et al. in view of Groh et al., Invitrogen, Lane et al. and Thermo Electron Corporation as applied to claim 7 above, and further in view of Sedelmeier. Claim 7 is rejected on the grounds set forth above. The teachings of the prior art are reiterated. While Lanzilli teaches gram negative cells, the art does not teach the use of E. coli as now recited in claim 1. Sedelmeier et al. teach a bacterial extract prepared from 18 selected E. coli strains that has been shown to protect against bacterial infections in mice (page 29, left column, first paragraph). The art teaches it has been described as a non-specific activator of the antimicrobial response (page 31, left column, second paragraph).The art demonstrate OM-89 acts as a specific immunogen in mice which is able to induce an immune response (see page 33, right column, last paragraph bridging first paragraph of page 34). It would have been obvious to one of ordinary skill in the art at the time of the Invention to try using E. coli gram negative bacteria in the method taught by Lanzilli. One would have been motivated to do so since Lanzilli teaches a method of making a bacteria extract and Sedelmeier teaches E. coli can be used to make bacteria extract. One would have had a reasonable expectation of success since Lanzilli teaches gram negative bacteria can be used in the disclosed method. One would have expected similar results since both references bacteria extracts used to provide an immune response. Therefore claim 15 is rendered obvious as claimed. Therefore Applicant’s Invention is rendered obvious as claimed. Claim 22 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Lanzilli et al. in view of Sedelmeier et al., Groh et al., Invitrogen and Lane et al. as applied to claim 1 above, and further in view of Shimizu et al. (The Laboratory Mouse (Routes of Administration. December 2004 (pp.527-542). Claim 1 is rejected on the grounds set forth above. The teachings of the prior art are reiterated. Lanzilli teaches administration to a subject. Sedelmeir teaches Sedelemeir teaches injecting a mouse (a subject). The art does not explicitly teach intravenous injection. Shimizu teaches intravenous injection is the most common route to inject substance solution or suspension into a mouse (see page 529, left column, first paragraph; page 534, left column, second paragraph). The art teaches the most rapid absorption is achieved by intravenous administration (same cited section). It would have been obvious to administer the composition by intravenous administration. One would have been motivated to do so since Sedelmeir treats a mouse and Shimizu teaches intravenous administration is the most rapid absorption is achieved by intravenous administration. One would have had a reasonable expectation of success since Shimizu teaches intravenous injection is the most common route to inject substance solution or suspension into a mouse. Therefore claim 22 is rendered obvious. APPLICANT’S ARGUMENTS The arguments made in the response filed on 11 November 2025 are acknowledged. New grounds of rejection have been necessitated by claim amendment. 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 extension fee 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 date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (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 an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the APIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000. /NATALIE M MOSS/ Examiner, Art Unit 1653 /SHARMILA G LANDAU/ Supervisory Patent Examiner, Art Unit 1653
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Prosecution Timeline

Jul 27, 2015
Application Filed
Jul 27, 2015
Response after Non-Final Action
Jan 31, 2017
Non-Final Rejection — §103, §112
Jun 06, 2017
Response Filed
Sep 06, 2017
Final Rejection — §103, §112
Nov 13, 2017
Response after Non-Final Action
Jan 16, 2018
Response after Non-Final Action
Feb 13, 2018
Request for Continued Examination
Feb 19, 2018
Response after Non-Final Action
Apr 02, 2018
Applicant Interview (Telephonic)
Jul 13, 2018
Non-Final Rejection — §103, §112
Oct 19, 2018
Response Filed
Mar 22, 2019
Final Rejection — §103, §112
May 28, 2019
Response after Non-Final Action
Jun 03, 2019
Response after Non-Final Action
Jun 28, 2019
Request for Continued Examination
Jun 29, 2019
Response after Non-Final Action
Mar 19, 2020
Non-Final Rejection — §103, §112
Jun 24, 2020
Response Filed
Dec 09, 2020
Final Rejection — §103, §112
Feb 14, 2021
Response after Non-Final Action
Mar 04, 2021
Request for Continued Examination
Mar 06, 2021
Response after Non-Final Action
May 22, 2021
Non-Final Rejection — §103, §112
Sep 27, 2021
Response Filed
Dec 07, 2021
Final Rejection — §103, §112
Feb 13, 2022
Response after Non-Final Action
Mar 14, 2022
Request for Continued Examination
Mar 15, 2022
Response after Non-Final Action
May 21, 2022
Non-Final Rejection — §103, §112
Aug 24, 2022
Response Filed
Aug 29, 2022
Applicant Interview (Telephonic)
Aug 29, 2022
Examiner Interview Summary
Dec 03, 2022
Final Rejection — §103, §112
Mar 02, 2023
Notice of Allowance
Mar 02, 2023
Response after Non-Final Action
May 03, 2023
Response after Non-Final Action
Jun 01, 2023
Applicant Interview (Telephonic)
Jun 01, 2023
Examiner Interview Summary
Jun 07, 2023
Response after Non-Final Action
Oct 12, 2023
Response after Non-Final Action
Dec 19, 2023
Response after Non-Final Action
Dec 19, 2023
Response after Non-Final Action
Dec 26, 2023
Response after Non-Final Action
Dec 27, 2023
Response after Non-Final Action
Dec 27, 2023
Response after Non-Final Action
Jan 03, 2024
Response after Non-Final Action
May 13, 2024
Response after Non-Final Action
May 29, 2024
Response after Non-Final Action
May 31, 2024
Response after Non-Final Action
Jul 31, 2024
Request for Continued Examination
Aug 04, 2024
Response after Non-Final Action
Mar 08, 2025
Non-Final Rejection — §103, §112
Jun 10, 2025
Response after Non-Final Action
Jun 10, 2025
Response Filed
Nov 11, 2025
Response Filed
Mar 10, 2026
Final Rejection — §103, §112 (current)

Precedent Cases

Applications granted by this same examiner with similar technology

Patent 12576116
USE OF PROBIOTICS IN THE TREATMENT AND/OR PREVENTION OF ATOPIC DERMATITIS
2y 5m to grant Granted Mar 17, 2026
Patent 12115199
Delivery System and Probiotic Composition for Animals and Plants
2y 5m to grant Granted Oct 15, 2024
Patent 12005089
CVS TRANSPLANTATION FOR TREATMENT OF BACTERIAL VAGINOSIS
2y 5m to grant Granted Jun 11, 2024
Patent 11262362
2-HYDROXYGLUTARATE AS A BIOMARKER FOR CHRONIC HYPOXIA
2y 5m to grant Granted Mar 01, 2022
Patent 11235003
PHARMACEUTICAL PREPARATION COMPRISING SUPERNATANT OF BLOOD MONONUCLEAR CELL CULTURE
2y 5m to grant Granted Feb 01, 2022
Study what changed to get past this examiner. Based on 5 most recent grants.

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Prosecution Projections

13-14
Expected OA Rounds
31%
Grant Probability
50%
With Interview (+18.4%)
3y 3m
Median Time to Grant
High
PTA Risk
Based on 509 resolved cases by this examiner. Grant probability derived from career allow rate.

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