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 .
Claim Status
The amended claim set filed on 2 February 2026 is acknowledged. Claims 2, 4-5, 11-16, 19-24, 26-27, 30-37, 39-40, 45-46, and 51-52 are currently pending. Of those, claims 2, 4-5, and 12-14 are amended. Claims 51-52 are new, and claims 19-24, 26-27, 30-37, 39-40, and 45-46 are withdrawn. Claims 1, 3, 6-10, 17-18, 25, 28-29, 38, 41-44, and 47-50 are cancelled. Claims 2, 4-5, 11-16, and 51-52 will be examined on the merits herein.
Response to Amendment
The Applicants’ arguments filed 2 February 2026 are acknowledged. For clarity, in this action, said arguments will be referred to as “Remarks” and the Non-Final Office Action mailed 2 October 2025 will be referred to “NFOA”.
Objection(s) and Rejection(s) Withdrawn
The objection to the specification is withdrawn in view of the amendments to the specification filed 2 February 2026.
The objection to claim 2 is withdrawn in view of the amendments to the claims.
The rejection of claim 12 under 35 U.S.C. 112(b) is withdrawn in view of the amendments to the claims.
The rejection of claims 2, 4-5, and 11-16 under 35 U.S.C. 102(a)(2) is withdrawn in view of the amendments to the claims.
Priority
Applicant argues (Remarks, pg. 8), “claims encompassing a composition comprising a lysate of Faecalibacterium prausnitzii and or a lysate of Bacteroides thetaiotaomicron (e.g., 13 and 51) have a proper claim of priority to U.S. Provisional Application No. 63/068,127.”
This argument has been fully considered but is not persuasive. MPEP 211.05(I)(A) states: “Under 35 U.S.C. 119(e), the written description and drawing(s) (if any) of the provisional application must adequately support and enable the subject matter claimed in the nonprovisional application that claims the benefit of the provisional application.” Dependent claim 13 includes both a Gram-positive and Gram-negative cell lysate. The claim does not limit both lysates within the scope of what is disclosed in the provisional application. As stated in para. 5 of the NFOA, Provisional Application 63/068,127 does not provide sufficient support for the full scope of claim 2. Thus, Provisional Application 63/068,127 does not provide sufficient support for claim 13. However, claim 51 is supported by the priority application because it limits both Gram-positive and Gram-negative cell lysate to match what is disclosed in the provisional application; thus, the effective filing date of claim 51 is 20 August 2020. The effective filing date of claims 2, 4-5, 11-16, and 52 is 20 August 2021.
New Rejection(s)
Claim Rejections - 35 USC § 103
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
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 2, 4, 11-16, and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Seo et al. (published 27 October 2020, KR 102169794 B1; herein “Seo”) as evidenced by Sigma-Aldrich (“Phosphate Buffered Saline (PBS)”) and Gunn et al. (WO 2022/198322 A1, effectively filed 24 March 2021; herein “Gunn”) in view of Goletz et al. (2013, UA 103153 C2; herein “Goletz”) as evidenced by Coats et al. (2011, Infect. Immun.; herein “Coats”).
Regarding claims 2, 13, and 51, Seo teaches a pharmaceutical composition for the prevention or treatment of liver disease, including liver cancer, comprising a lysate of F. prausnitzii EB-FPDK11 strain (para. 18-19) and a suitable carrier or excipient (para. 25-26). Seo also teaches that the composition may be consumed as an adjuvant to enhance the effects of preventing or improving liver diseases (para. 35).
Regarding claim 11, Seo teaches that the F. prausnitzii strain is a gut bacterium (para. 13); therefore, the CpG abundance of the F. prausnitzii strain is substantially similar to that of a gut bacterium.
Regarding claim 12, the composition comprises lipoteichoic acid (LTA) having a structure of LTA found in F. prausnitzii because the composition comprises F. prausnitzii (para. 8).
Regarding claim 14, F. prausnitzii is a Gram-positive bacterium; therefore, it inherently contains lipoteichoic acid, which is recognized by TLR2 and peptidoglycan, which is recognized by NOD2, as is evidenced by Gunn (para. 35-36 and 42 and Table 1).
Regarding claim 15-16, Seo teaches that the composition may be in a liquid (para. 16 and 30) and that the composition may comprise PBS (para. 134), which has a pH of 7-7.4 and prevents changes in pH in a solution (as evidenced by Sigma-Aldrich, top paragraph).
However, Seo does not teach a pharmaceutical composition comprising one or more bacterial lysates from one or more species of a Gram-negative bacterial cell, as in claim 2, wherein the composition comprises a bacterial lysate of B. thetaiotaomicron, a bacterial lysate of B. vulgatus, or a combination thereof, as in claim 4, a pharmaceutical composition wherein the one or more species of a Gram-negative bacterial cell comprises a monophosphoryl Lipid A comprising 5-6 acyl chains such that the Gram-negative bacterial lysate comprises the same, as in claim 11, a lysate containing ligands capable of binding toll-like receptor 4 on a target cell, as in claim 14, or a bacterial lysate of B. thetaiotaomicron, as in claim 51.
Regarding claims 2, 4, and 51, Goletz teaches a composition comprising at least one lysate of Bacteroides microorganisms, including Bacteroides thetaiotaomicron and/or Bacteroides ovatus (pg. 124-125, claims 1 and 5). Goletz also teaches that this composition may be used to create or enhance a humoral and/or cellular immune response to SorE-1 positive tumor cells thereby treating or preventing SorE-1 positive tumors (pg. 127, claims 20-21), which includes tumors in the liver, stomach, and colon (pg. 4, para. 5-6).
Regarding claims 11 and 14, B. thetaiotaomicron produces a penta-acylated monophosphoryl lipid A, which is recognized by TLR4, thereby stimulating an immune response, as evidenced by Coats (Abstract).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to combine the pharmaceutical composition comprising F. prausnitzii lysate taught by Seo with the composition comprising B. thetaiotaomicron and B. ovatus lysates taught by Goletz, thereby arriving at the invention of claims 2, 4, 11-16, and 51. The person of ordinary skill in the art would have been motivated to make the modification because the composition of Goletz may be used to treat or prevent liver cancer and the composition of Seo may be used as an adjuvant to enhance the effects of preventing or improving liver cancer. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because both compositions are known to treat liver cancer. Therefore, the combination leads to expected results because each element performs the same function as is does individually. The compositions of Seo and Goletz are both made for the purpose of treating liver cancer. From MPEP 2144.06(I): "'It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose .... [T]he idea of combining them flows logically from their having been individually taught in the prior art.' In re Kerkhoven, 626 F.2d 846,850,205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) .... "
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., Gram-positive bacterial lysate, F. prausnitzii, Gram-negative bacterial lysate, B. thetaiotaomicron, and B. ovatus) were known in the art. In addition, combining these elements yields a composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claim(s) 2, 4-5, 11-16, and 51 are rejected under 35 U.S.C. 103 as being unpatentable over Seo (published 27 October 2020, KR 102169794 B1) as evidenced by Sigma-Aldrich (“Phosphate Buffered Saline (PBS)”) and Gunn (WO 2022/198322 A1, effectively filed 24 March 2021) in view of Goletz (2013, UA 103153 C2) as evidenced by Coats (2011, Infect. Immun.) as applied to claims 2, 4, and 11-16 above, and further in view of Lee et al. (2019, KR 102053730 B1; herein “Lee”).
The combination of Seo and Goletz is set forth in para. 12-22 above and teaches all elements of claims 2, 4, 11-16, and 51.
Seo also teaches that the composition comprising a lysate of F. prausnitzii EB-FPDK11 strain (para. 18-19) may be used for the prevention or treatment of inflammatory diseases (para. 14 and 17).
Regarding claims 2 and 5, Lee teaches a functional food composition for improving inflammation comprising Enterococcus faecalis lysate (para. 19 and 25). Lee also teaches that Enterococcus faecalis is a probiotic bacterium, which can enhance an immune response against cancer (para. 9-10 and 13).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to combine the composition comprising F. prausnitzii, B. thetaiotaomicron, and B. ovatus lysates taught by Seo and Goletz with the E. faecalis lysate taught by Lee, thereby arriving at the invention of claims 2, 4-5, and 11-16. The person of ordinary skill in the art would have been motivated to make the modification because the lysates of F. prausnitzii and E. faecalis can be used for their anti-inflammatory properties and can be used as adjuvants or probiotics to enhance the immune response against cancers. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of successfully combining the bacterial lysate compositions because the lysate compositions of Seo and Lee may be used as anti-inflammatory compositions and to improve the immune response against cancer, such as that caused by the lysate composition of Goletz. Therefore, the combination leads to expected results because each element performs the same function as is does individually. The compositions of Seo and Lee are both made for the purpose of reducing inflammation. From MPEP 2144.06(I): "'It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose .... [T]he idea of combining them flows logically from their having been individually taught in the prior art.' In re Kerkhoven, 626 F.2d 846,850,205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) .... "
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., Gram-positive bacterial lysate, F. prausnitzii, Gram-negative bacterial lysate, B. thetaiotaomicron, B. ovatus, and E. faecalis) were known in the art. In addition, combining these elements yields a composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Claim(s) 2, 4, 11-16, and 51-52 are rejected under 35 U.S.C. 103 as being unpatentable over Seo (published 27 October 2020, KR 102169794 B1) as evidenced by Sigma-Aldrich (“Phosphate Buffered Saline (PBS)”) and Gunn (WO 2022/198322 A1, effectively filed 24 March 2021) in view of Goletz (2013, UA 103153 C2) as evidenced by Coats (2011, Infect. Immun.) as applied to claims 2, 4, and 11-16 above, and further in view of Laborda-Illanes et al. (2020, Cancers; herein “Laborda-Illanes”) and Wang et al. (2012, ISME J.; herein “Wang”).
The combination of Seo and Goletz is set forth in para. 12-22 above and teaches all elements of claims 2, 4, 11-16, and 51.
However, neither Seo nor Goletz teaches a bacterial lysate of B. producta or B. vulgatus, as in claim 52.
Regarding claims 2, 4, and 52, Laborda-Illanes teaches that colonization by Blautia producta in the gut of rats had protective effects against breast cancer development (pg. 16, para. 1).
Regarding claims 2 and 52, Wang teaches that mice which have been colonized by B. vulgatus have significantly reduced colitis-associated colorectal tumor multiplicity (pg. 327, left col., para. 1).
Regarding claim 2, Zolkiewicz teaches that bacterial lysates (BLs) stimulate dendritic cells (DCs) and subsequently activate T and B lymphocytes (section 2.6, para. 1). Zolkiewicz also teaches that bacterial lysates mimic the presence of bacteria, which stimulate the immune system (section 2.6, para. 2). Zolkiewicz also teaches that the safety of bacterial lysates has been confirmed in many clinical studies (section 2.6, para. 2).
Therefore, it would have been prima facie obvious, before the effective filing date of the claimed invention, to a person of ordinary skill in the art, to modify the composition of Seo and Goletz to comprise bacterial lysates of B. producta and B. vulgatus, thereby resulting in the invention of claims 2, 4, 11-16, and 52. The person of ordinary skill in the art would have been motivated to make the modification because colonization by B. producta and B. vulgatus are shown to protect against cancer development and because bacterial lysates are capable of stimulating DCs and T and B lymphocytes, as is taught by Zolkiewicz. Therefore, the combination is also desirable (see MPEP 2144(II)). The person of ordinary skill in the art would have had a reasonable expectation of success because Zolkiewicz teaches that bacterial lysates mimic the presence of bacteria, so one would predict that lysates of the bacteria taught by Laborda-Illanes and Wang would have the same beneficial characteristics as the composition comprising whole cells and be at least as effective in protecting against cancer. Therefore, the combination leads to expected results because each element performs the same function as is does individually.
Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that combining prior art elements according to known methods to yield predictable results, is obvious unless its application is beyond that person's skill. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results. In the instant case, all elements (i.e., gram-positive and gram-negative bacterial lysates, B. producta, B. vulgatus, etc.) were known in the art. In addition, combining these elements yields a composition wherein each element merely performs the same function as it does separately; thus, the results of the combination would be recognized as predictable to one of ordinary skill in the art. Therefore, the claimed invention is prima facie obvious in view of the teachings of the prior art, absent any convincing evidence to the contrary.
Conclusion
No claim is 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BAILEY M MORGAN whose telephone number is (703)756-5388. The examiner can normally be reached M-F 9-5 ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, SAMIRA JEAN-LOUIS can be reached at (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BAILEY M MORGAN/Examiner, Art Unit 1645
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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