Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Applicant’s amendment filed on 20 May 2026 is entered. Claims 9-10 and 15 are amended. Claims 1-10 and 15 are pending. Claims 1-8 are withdrawn. Claims 9, 10 and 15 are under examination.
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 9-10 and 15 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 claim(s) contains 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 9 recites the limitation “wherein the peptidoglycan is directly administered to nasopharyngeal carcinoma cells”, which is new matter. This limitation lacks support in the original disclosure as filed on 22 July 2022.
The specification does not disclose administering peptidoglycan directly to nasopharyngeal carcinoma cells. Although the specification describes administering heat-killed whole bacterial liquids of Lactobacillus paracasei GMNL-653 to NPC-BM1 nasopharyngeal carcinoma cells (Specification pg. 20 para. 1), this administration does not specifically administer purified peptidoglycan directly to the cancer cells as claim 9’s limitation requires.
Embodiment 15 of the specification and Figure 16 discloses that peptidoglycan (10 microg, 20 microg, and 50 microg) was administered to NPC-BM1 nasopharyngeal carcinoma cell lines (Specification pgs. 43-44) , which are proliferated in vitro, not in a patient. However, there is no description that the purified peptidoglycan was purified from Lactobacillus paracasei GMNL-653, and in the same method to treat nasopharyngeal carcinoma after the peptidoglycan is administered to a patient by injection, as is required in claim 9. There is no description of a method of purifying peptidoglycan from Lactobacillus paracasei GMNL-653, thus the administered peptidoglycan is not described to have a definitive source, as required by the limitation.
Thus, the limitation “wherein the peptidoglycan is directly administered to nasopharyngeal carcinoma cells” in claim 9 is considered to be new matter. Claims 10 and 15 are dependent on claim 9, so also contain new matter.
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 9-10 and 15 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 9 recites “wherein the peptidoglycan is administered to a patient by injection” and also recites “wherein the peptidoglycan is directly administered to nasopharyngeal carcinoma cells”. The two limitations require the administration of the purified peptidoglycan to two different entities. It is unclear whether the nasopharyngeal carcinoma cells are located on skin surface, underneath the skin of the patient, or ex vivo in a cell culture dish where the purified peptidoglycan is to be directly administered, in order to meet the requirement of administering the peptidoglycan to a patient by injection.
Claims 10 and 15 are dependent on claim 9, so are indefinite for the same reason.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Park et al. (WO 2022265447 A1, effectively filed 18 June 2021) in view of Wang et al. (Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions: from C. elegans to mice, GeroScience (2020) 42:333-352, published 08 December 2019), and Chen et al. (US 20180256654 A1, published September 13, 2018) and as evidenced by Cleveland Clinic (Nasopharyngeal Cancer, https://my.clevelandclinic.org/health/diseases/21661-nasopharyngeal-cancer, accessed 20 June 2025).
Claim 9 recites the nasopharyngeal carcinoma is treated by inducing pyroptosis or cell cycle arrest in nasopharyngeal carcinoma cells”, which is a functional limitation that is interpreted as being an intended outcome of practicing the claimed method, but does not add any new active steps to the method; thus, where the prior art teaches the claimed method of treating nasopharyngeal carcinoma with an effective dosage of purified peptidoglycan or lipoteichoic acid of Lactobacillus paracasei GMNL-653 comprising administering the purified peptidoglycan or lipoteichoic acid by injection directly to the nasopharyngeal carcinoma cells, claim 9 is considered to be rendered obvious.
Regarding claim 9, Park teaches the injection of Lactobacillus paracasei into colorectal cancer and breast cancer models to test the anti-cancer activity of the Lactobacillus paracasei,and confirmed the Lactobacillus paracasei is suitable to treat colorectal and breast cancers (Park pg. 12 Example 3-2). Park continues to test the anti-cancer activity of Lactobacillus paracasei by treating various other cancer types, including pancreatic cancer, gallbladder cancer, kidney cancer, colon cancer, lung cancer, liver cancer, skin cancer, breast cancer, and stomach cancer. The Lactobacillus paracasei cells were administered to the cultures of different cancer cells, and Park confirmed the excellent anti-cancer activity of Lactobacillus paracasei against a broad amount of cancers in a variety of organs (Park pgs. 13-14 Example 5). Furthermore, Park teaches the Lactobacillus paracasei can be attenuated dead strains (Park pg. 5 para. 7). Park teaches the cancers suitable to be treated by Lactobacillus paracasei include head or neck cancers (Park pg. 5 para. 9). Nasopharyngeal carcinoma is a head and neck cancer, as evidenced by Cleveland Clinic (pg. 3 sent. 1).
However, Park does not teach administration of an effective dosage of purified peptidoglycan of Lactobacillus paracasei GMNL-653.
Wang teaches the administration of purified peptidoglycan isolated from Lactobacillus paracasei to a cell culture, as well as administration of cell wall extractions containing peptidoglycan isolated from Lactobacillus paracasei in a cell culture (Wang pg. 341 para. 2, and figs. 6 and 7). Wang teaches fractionation and purification procedures for peptidoglycan from Lactobacillus paracasei cells and culture supernatants (Wang Pg. 341 para. 2, and pg. 349 paras. 2-3).
Chen teaches a composition comprising Lactobacillus paracasei GMNL-653 (Chen claim 1).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to treat nasopharyngeal carcinoma by injecting purified peptidoglycan isolated from Lactobacillus paracasei GMNL-653 cells into the nasopharyngeal carcinoma cancer cells. It would have been further obvious to substitute Chen’s Lactobacillus paracasei GMNL-653 for Wang’s Lactobacillus paracasei D3-5 for purification of peptidoglycan. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because Park teaches the injection of Lactobacillus paracasei strains into cancer cells, and the superiority of Lactobacillus paracasei strains in treating a variety of cancer types, including head and neck cancers such as nasopharyngeal cancer, Chen teaches one such strain of Lactobacillus paracasei, GMNL-653, and Wang teaches administering purified peptidoglycan isolated from Lactobacillus paracasei cells to target cells, as well as procedures for isolating and purifying peptidoglycan from Lactobacillus paracasei cell cultures.
Regarding claim 10, claim 10 recites “wherein the nasopharyngeal carcinoma is not treated by inducing apoptosis in nasopharyngeal carcinoma cells”, which is a negative limitation that does not add any new active steps to the method; thus, where the prior art teaches the claimed method of treating nasopharyngeal carcinoma with peptidoglycan of Lactobacillus paracasei GMNL-653, claim 10 is considered to be rendered obvious.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Park in view of Chen and Park as applied to claims 9-10 above, and further in view of Tanny et al. (Improved Filtration Technique for Concentrating and Harvesting Bacteria, Applied and Environmental Microbiology, Aug. 1980, p. 269-273 Vol. 40, No. 2).
Park, Chen, and Wang do not teach an effective dosage of purified peptidoglycan of Lactobacillus paracasei GMNL-653 ranging from 10 µg/ml to 50 µg/ml.
MPEP §2144.05(II)(A) states “[g]enerally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”.
MPEP §2144.05(II)(B) states “[i]n order to properly support a rejection on the basis that an invention is the result of "routine optimization", the examiner must make findings of relevant facts, and present the underpinning reasoning in sufficient detail. The articulated rationale must include an explanation of why it would have been routine optimization to arrive at the claimed invention and why a person of ordinary skill in the art would have had a reasonable expectation of success to formulate the claimed range. See In re Stepan, 868 F.3d 1342, 1346, 123 USPQ2d 1838, 1841 (Fed. Cir. 2017).
Park teaches that the culture of the Lactobacillus paracasei treatment can be a concentrated culture solution, a concentrated culture filtrate, or a concentrated solution (Park pg. 4 para. 6), but does not teach a means of concentrating the cultures, nor peptidoglycan.
Wang teaches fractionation and purification procedures for peptidoglycan from Lactobacillus paracasei cells and culture supernatants (Wang Pg. 341 para. 2, and pg. 349 paras. 2-3), and that the peptidoglycan can be used to treat cells in concentrations of 1% (v/v) (Wang pg. 349 para. 2-3), but does not teach a means of modulating the concentration of peptidoglycan.
Tanny teaches that bacterial cultures can be concentrated using filtration techniques (Tanny abstract).
It would be obvious to one of ordinary skill in the art to optimize the concentration of purified peptidoglycan of Lactobacillus paracasei GMNL-653 in order to produce an optimum treatment effect on nasopharyngeal carcinoma. One of ordinary skill in the art would have had a reasonable expectation of success because methods of modulating peptidoglycan concentrations were well known in the prior art. Peptidoglycan concentrations are directly proportional to the amount of Lactobacillus paracasei GMNL-653 cells in culture because peptidoglycan is a component in Lactobacillus paracasei cell walls as taught by Wang, so the concentration of peptidoglycan can be adjusted by concentrating the Lactobacillus paracasei cells in culture of Park by using the filtration method of Tanny, and fractioning and purifying the peptidoglycan from those Lactobacillus paracasei GMNL-653 cells using the procedures taught by Wang. One of ordinary skill in the art would begin optimization of the peptidoglycan concentrations by starting at the 1%(v/v) taught by Wang.
Response to Arguments
Applicant's arguments filed 20 May 2026 have been fully considered but they are not persuasive.
Regarding Applicant’s arguments that it is unexpected that purified peptidoglycan from Lactobacillus paracasei GMNL-653 shows stronger cancer inhibition as compared to Lactobacillus paracasei GMNL-653 whole bacteria (Remarks pg. 6-9 and Figs. 1 and 16), it is not unexpected to one of ordinary skill in the art that peptidoglycan extracts from Lactobacillus paracasei show strong anticancer effects, as evidenced by Tian et al. (Extraction of Peptidoglycan from L. paracasei subp. paracasei X12 and Its Preliminary Mechanisms of Inducing Immunogenic Cell Death in HT-29 Cells, Int. J. Mol. Sci. 2015, 16, 20033-20049; doi: 10.3390/ijms160820033), Liu et al. (Anti-cancer Substances and Safety of Lactic Acid Bacteria in Clinical Treatment, Front. Microbiol. 12:722052. doi: 10.3389/fmicb.2021.722052), and Wang et al. 2017 (Whole Peptidoglycan Extracts from the Lactobacillus paracasei subsp. paracasei M5 Strain Exert Anticancer Activity In Vitro, BioMed Research International Volume 2018, Article ID 2871710, 11 pages, https://doi.org/10.1155/2018/2871710).
Tian teaches that peptidoglycan extracts from Lactobacillus paracasei have an anticancer effect by inducing cell death (Tian abstract).
Liu teaches that peptidoglycan from several species of lactic acid bacteria has known anti-cancer effects, including Lactobacillus paracasei through an ER-targeted immunogenic cell death pathway (Liu pg. 4-5 sec. Peptidoglycan).
Wang 2017 teaches that whole peptidoglycan extracted from a Lactobacillus paracasei strain had cytotoxic effects on HT-29 cancer cells in a dose-dependent manner, upregulated proapoptotic genes, and downregulated antiapoptotic genes, thus demonstrating the peptidoglycan fraction had strong anticancer effects (Wang 2017 Abstract).
One of ordinary skill in the art would not be surprised that a peptidoglycan extraction from a strain of Lactobacillus paracasei known to have anticancer effects would exhibit strong anticancer effects on its own. Thus, one of ordinary skill in the art would not find Applicant’s results unexpected.
Conclusion
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/Alexander M Duryee/Examiner, Art Unit 1657
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
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