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 24 September 2025 has been entered. Claims 1-10 and 15 are pending. Claims 1-8 are withdrawn.
Claims 9, 10 and 15 are under examination.
Claim Objections
Claims 10 and 15 are objected to because of the following informalities:
In claim 10, the word “to” in line 2 is extraneous and should be deleted.
In claim 15, the word “thereof” in line 3 is extraneous and should be deleted.
Appropriate correction is required.
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 10 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.
(Maintained) Claim 10 recites the nasopharyngeal carcinoma is not treated by inducing to apoptosis in nasopharyngeal carcinoma cells. The grammatical sentence structure is 1) “the nasopharyngeal carcinoma” is the direct object i.e. the object the verb phrase is acting on, 2) “not treated by inducing to apoptosis” is the verb phrase, and 3) “in nasopharyngeal carcinoma cells” is the locative noun indicating where the sentence happens. The word order of a sentence in English is subject-verb-object (SVO), and the subject performs a verb on a direct object. In the recited limitation, the word order is incorrect and the subject appears to be omitted (the direct object is first, the verb is second, and the subject is not present).
The limitation “wherein the nasopharyngeal carcinoma is not treated by inducing to apoptosis in nasopharyngeal carcinoma cells” is unclear because the phrase limits the nasopharyngeal carcinoma disease to be induced to apoptosis. In other words, the verb phrase “not inducing to apoptosis” is acting on the nasopharyngeal carcinoma disease not on the nasopharyngeal carcinoma cells. As currently written, the locative phrase “in nasopharyngeal carcinoma cells” merely indicates where the sentence is occurring. Apoptosis is a noun meaning a process of programmed cell death that occurs in cells. However, nasopharyngeal carcinoma is a disease which is a state of being for an individual, not a cell or collection of cells. The nasopharyngeal carcinoma disease does not have a process of apoptosis that can be induced because it is not a cell. It is therefore unclear how apoptosis can be induced in the nasopharyngeal carcinoma disease when the process of apoptosis is required to occur within cells.
It is suggested to amend claim 10 to recite delete the confounding word “to” such that the limitation would read “wherein the nasopharyngeal carcinoma is not treated by inducing apoptosis in nasopharyngeal carcinoma cells” or “wherein the peptidoglycan or lipoteichoic acid does not induce apoptosis in nasopharyngeal carcinoma cells” in order to obviate this rejection.
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.
(Modified to address claim amendment) 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 the 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 or lipoteichoic acid of Lactobacillus paracasei GMNL-653.
Wang teaches the administration of purified peptidoglycan and lipoteichoic acid isolated from Lactobacillus paracasei to a cell culture, as well as administration of cell wall extractions containing both peptidoglycan and lipoteichoic acid 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 both peptidoglycan and lipoteichoic acid, and the combination thereof, 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 and lipoteichoic acid 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 or lipoteichoic acid. 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 and/or lipoteichoic acid isolated from Lactobacillus paracasei cells to target cells, as well as procedures for isolating and purifying peptidoglycan and/or lipoteichoic acid from Lactobacillus paracasei cell cultures.
Regarding claim 10, claim 10 recites “wherein the nasopharyngeal carcinoma is not treated by inducing to apoptosis 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 peptidoglycan or lipoteichoic acid in heat-killed whole-bacterial liquids of Lactobacillus paracasei GMNL-653 comprising administering the heat-killed whole-bacterial liquids by injection directly to the nasopharyngeal carcinoma cells, claim 10 is considered to be rendered obvious.
(Maintained) 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 or lipoteichoic acid 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 or lipoteichoic acid.
Wang teaches fractionation and purification procedures for both peptidoglycan and lipoteichoic acid, and the combination thereof, from Lactobacillus paracasei cells and culture supernatants (Wang Pg. 341 para. 2, and pg. 349 paras. 2-3), and that the cell wall components peptidoglycan and lipoteichoic acid 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 concentrations of peptidoglycan and lipoteichoic acid.
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 and lipoteichoic acid 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 and lipoteichoic acid concentrations were well known in the prior art. Peptidoglycan and lipoteichoic acid concentrations are directly proportional to the amount of Lactobacillus paracasei GMNL-653 cells in culture because peptidoglycan and lipoteichoic acid are components in Lactobacillus paracasei cell walls as taught by Wang, so the concentrations of peptidoglycan and lipoteichoic acid 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 and lipoteichoic acid 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 or lipoteichoic acid concentrations by starting at the 1%(v/v) taught by Wang.
Response to Arguments
Applicant's arguments filed 24 September 2025 have been fully considered but they are not persuasive.
Regarding Applicant’s arguments that the term in claim 10 as amended fixes the indefinite grammatical issues (Remarks pg. 6 para. 2), the claim has grammar issues, and is still indefinite. The word “to” in the limitation “wherein the nasopharyngeal carcinoma is not treated by inducing to apoptosis in nasopharyngeal carcinoma cells” still reads that the apoptosis is being induced in the nasopharyngeal carcinoma disease itself, not in the cells. If Applicant deletes the word “to”, the claim would then clearly read that the action of “inducing apoptosis” is being performed on the nasopharyngeal carcinoma cells, not the disease, and that the nasopharyngeal carcinoma disease is not being treated by this induction of apoptosis in the nasopharyngeal carcinoma cells.
Regarding Applicant’s arguments that Park’s broad teaching of the types of cancers their invention can treat doesn’t indicate that Park’s invention can treat any kind of cancer, including head/neck cancers like nasopharyngeal carcinoma, and that Park only shows anticancer effects on other types of cancer other than head/neck cancers like nasopharyngeal carcinoma (Remarks pgs. 6-8 sec. 1), although Park does disclose a broad array of cancer types their invention can treat, Park does nonetheless disclose that head and neck cancers are treatable by their invention, and nasopharyngeal carcinoma is a head and neck cancer, as evidenced by Cleveland Clinic (pg. 3 sent. 1).
There is no evidence of record that shows Park’s invention is ineffective to treat head/neck cancers like nasopharyngeal carcinoma. Therefore, based on the preponderance of evidence and the disclosure of Park, it would be apparent to one of ordinary skill in the art that Park’s method of treating cancers by injecting Lactobacillus paracasei into the cancer cells would be effective to treat head/neck cancers like nasopharyngeal carcinoma.
Regarding Applicant’s arguments that Lactobacillus paracasei GMNL-653 shows stronger anticancer effects on nasopharyngeal cancer cells as compared to Lactobacillus paracasei BCRC 910520 (Remarks pg. 8 sec. 2), Lactobacillus paracasei BCRC 910520 is not relied upon in the 103 rejection, nor is it recited in the claims. Furthermore, the claims no longer recite administration of Lactobacillus paracasei GMNL-653 cells to treat nasopharyngeal carcinoma. Additionally, Chen teaches Lactobacillus paracasei GMNL-653, and the combination of references Park, Chen, and Wang renders obvious the use of purified peptidoglycan and lipoteichoic acid from Lactobacillus paracasei GMNL-653 to treat nasopharyngeal carcinoma.
Regarding Applicant’s arguments that none of the cited references indicate the technical feature of the present invention, specifically that none of the cited references indicate directly administering purified peptidoglycan and lipoteichoic acid of Lactobacillus paracasei GMNL-653 to nasopharyngeal carcinoma cells without participation of immune system or digestive system (Remarks pg. 8-9 sec. 3), one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As written in the 103 rejection of claims 9-10 above, the rejection is based on the combination of Park, Chen, and Wang. When the teachings of Park, Chen, and Wang are considered collectively, 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 and lipoteichoic acid isolated from Lactobacillus paracasei GMNL-653 cells into the nasopharyngeal carcinoma cancer cells. 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 and/or lipoteichoic acid isolated from Lactobacillus paracasei cells to target cells, as well as procedures for isolating and purifying peptidoglycan and/or lipoteichoic acid from Lactobacillus paracasei cell cultures.
Regarding Applicant’s arguments that the purification method of the instant invention is different from that disclosed in Tanny (Remarks pgs. 9-10 sec. 4), the claims do not recite a method of purifying peptidoglycan and lipoteichoic acid from Lactobacillus paracasei GMNL-653. Thus, any differences between the purification methods of Applicant and Tanny are not relevant to the claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Regarding Applicant’s arguments that there are advantages of administering purified peptidoglycan and lipoteichoic acid of Lactobacillus paracasei GMNL-653 compared to administering bacteria and its culture (Remarks pg. pg. 10-11 sec. 5), the argument is moot and insufficient to overcome the prima facie case of obviousness because the instant invention and the 103 rejections are no longer drawn to administering Lactobacillus paracasei GMNL-653 cells themselves to treat nasopharyngeal carcinoma. Amended claim 9 now limits the method of treating nasopharyngeal carcinoma to administering purified peptidoglycan and lipoteichoic acid isolated from Lactobacillus paracasei GMNL-653 cells into the nasopharyngeal carcinoma cancer cells. As described in the 103 rejection above, when the teachings of Park, Chen, and Wang are considered collectively, 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 and lipoteichoic acid isolated from Lactobacillus paracasei GMNL-653 cells into the nasopharyngeal carcinoma cancer cells.
Conclusion
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 Alexander M Duryee whose telephone number is (571)272-9377. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
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/Alexander M Duryee/Examiner, Art Unit 1657
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657