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 23 June 2026 is entered. Claims 23-27 are new. Claims 3-4, 11-12, and 14-27 are pending.
Priority
Applicant’s claim for priority to the filing date of CN202111643716.X filed 29 December 2021 and PCT/CN2023/078812 filed 28 February 2023 is acknowledged. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
The effective filing date is 29 December 2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 28 June 2024 is being considered by the examiner.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 3-4 and 23-27, in the reply filed on 23 June 2026 is acknowledged.
Claims 11-12 and 14-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 23 June 2026.
Applicant's species election with traverse of inhibiting tumor volume growth, lung cancer, and a tumor in the reply filed on 23 June 2026 is acknowledged. The species elections are drawn to genera that are encompassed by the nonelected claims. Applicant’s traversal is on the grounds that the functions of the claimed oral pharmaceutical composition when used for, e.g., treating or preventing a disease such as tumor, have shared underlying mechanisms, such as promoting the expression of IFN-beta, exerting an anti-viral, anti-tumor, immunomodulatory, and other effects (see, e.g., Example 9 of the specification).
This is not found persuasive because the possibility of some shared underlying mechanisms does not make each of these species within the provided genera obvious variants of one another or link them under a single general inventive concept because the genus of means of inhibiting tumor growth exhibit different strategies and methods of inhibiting tumor growth, such as using acetic, propionic, or butyric acid to inhibit HDAC activity, or reducing anti-PD-1 drug resistance. There is no evidence provided which demonstrates these different species are obvious over one another. The different types of cancers recited in the genus of tumors are varied and encompass cancers of different tissues, pathogenesis, and treatment procedures. The genus of diseases mediated by HDAC activity are varied and encompass diseases of completely different tissues or systems within the body, such as central nervous system versus the gastrointestinal system.
The requirement is still deemed proper and is therefore made FINAL.
Claims 3-4 and 23-27 are under examination.
Claim Objections
Claim 26 is objected to because of the following informalities: There should be a space inserted between “50%” and “of” on line 2. Appropriate correction is required.
Biological Material
It is apparent that biological material Lachnospiraceae sp. MNH 46686 with deposit number of GDMCC No: 62002 is required to practice the claimed invention. Applicant has provided the information for the deposit of Lachnospiraceae sp. MNH 46686 at Guangdong Microbial Culture Collection Center on November 4, 2021, and Applicant states that all restrictions imposed by the depositor on the availability to the public of the biological material will be irrevocably removed upon the granting of a patent (Specification pg. 4-5 bridging para.). Thus, Examiner has determined that the biological material Lachnospiraceae sp. MNH 46686 with deposit number of GDMCC No: 62002 conforms to the requirements of Biological Deposits.
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.
Claims 3-4 and 23-27 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 3 recites that oral pharmaceutical composition comprises “a microbial strain of Lachnospiraceae; and a pharmaceutically acceptable carrier in an enteric coating”. It is unclear whether the enteric coating only coats the pharmaceutically acceptable carrier or coats both the microbial strain AND the pharmaceutically acceptable carrier.
Claims 4 and 23-27 are dependent on claim 3, so are indefinite for the same reason.
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 23 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 23 recites the oral pharmaceutical composition of claim 3 comprises viable cells, viable bacteria, attenuated bacteria, irradiated bacteria or inactivated bacteria of the microbial strain of Lachnospiraceae, a metabolite of the microbial strain of Lachnospiraceae, or a supernatant of the microbial strain of Lachnospiraceae. However, parent claim 3 recites the composition comprises a microbial strain of Lachnospiraceae, not a metabolite of the microbial strain of Lachnospiraceae or a supernatant of the microbial strain of Lachnospiraceae. Thus, claim 23 recites a broader genus of Lachnospiraceae than claimed in claim 3, so claim 23 fails to include all the limitations of the claim upon which it depends.
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 § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 3-4 and 23-27 are rejected under 35 U.S.C. 101 because the claimed invention is directed to the judicial exception of a product of nature without significantly more.
Claims 3-4 and 23-27 are drawn to the statutory category of a composition of matter (Step 1: Yes).
Claim 3 recites an oral pharmaceutical composition comprising: a microbial strain of Lachnospiraceae; and a pharmaceutically acceptable carrier in an enteric coating. Claim 4 recites that the microbial strain of Lachnospiraceae comprises Lachnospiraceae MNH 46686 strain with deposit number of GDMCC No: 62002. Lachnospiraceae sp. MNH 46686 with deposit number of GDMCC No: 62002 is a naturally occurring bacteria isolated from a stool sample of a healthy female volunteer (Specification pg. 34 para. 1). The BRI of the term “pharmaceutically acceptable carrier” includes natural compounds, such as water. The term “enteric coating” is not by itself non-natural, as there are examples of naturally occurring compounds act as enteric coatings such as alginate, as evidenced by the abstract of Habashy et al. (A Novel Multilayer Natural Coating for Fed-State Gastric Protection. Pharmaceutics. 2022 Jan 26;14(2):283. doi: 10.3390/pharmaceutics14020283).
Claim 23 recites the oral pharmaceutical composition comprises viable cells, viable bacteria, attenuated bacteria, irradiated bacteria or inactivated bacteria of the microbial strain of Lachnospiraceae, a metabolite of the microbial strain of Lachnospiraceae, or a supernatant of the microbial strain of Lachnospiraceae. As established above, Lachnospiraceae are naturally occurring bacteria, and retain their natural status regardless of whether they are viable, attenuated, irradiated, or inactivated. The BRI of metabolites and supernatants of the microbial strain of Lachnospiraceae includes any compound produced by or extractable from the microbial strain of Lachnospiraceae, which is includes natural compounds like water and proteins naturally produced by the microbial strain of Lachnospiraceae.
Claim 24 recites the oral pharmaceutical composition further comprises a co-drug; and the co-drug comprises at least one of a chemotherapeutic agent, photosensitizing agent, photothermal agent, immunotherapeutic agent, or an agent for enhancing cell therapy; and the immunotherapeutic agent comprises an Anti-PD-1 antibody, CTLA-4 antibody, PD-L1 antibody, or PD-L1 inhibitor.
The BRI of chemotherapeutic agents includes naturally occurring compounds that have anti-cancer effects, including plant alkaloids, toxoids, and podophyllotoxins, as evidenced by the abstract of Demain et al. (Natural products for cancer chemotherapy. Microb Biotechnol. 2011 Nov;4(6):687-99. doi: 10.1111/j.1751-7915.2010.00221.x. Epub 2010 Nov 18. PMID: 21375717; PMCID: PMC3815406). The BRI of photosensitizing agents includes naturally occurring compounds that can be extracted from plants like furanocoumarins, polyacetylenes, thiophenes, tolyporphins, curcumins, alkaloid and anthraquinones, as evidenced by the abstract of Kubrak et al. (Some Natural Photosensitizers and Their Medicinal Properties for Use in Photodynamic Therapy. Molecules. 2022 Feb 10;27(4):1192. doi: 10.3390/molecules27041192. PMID: 35208984; PMCID: PMC8879555). The BRI of photothermal agents includes naturally occurring compounds such as melanin, as evidenced by the abstract of Menichetti et al. (Melanin as a Photothermal Agent in Antimicrobial Systems. Int J Mol Sci. 2024 Aug 18;25(16):8975. doi: 10.3390/ijms25168975. PMID: 39201661; PMCID: PMC11354747). The BRI of immunotherapeutic agents, including PD-L1 inhibitors, include naturally occurring chemical compounds, such as apigenin or cosmosiin extracted from traditional medicine plant Salvia plebeia R. BR, as evidenced by pg. 3 sec. 2.1 para. 1 of Nakhjavani et al. (Natural Blockers of PD-1/PD-L1 Interaction for the Immunotherapy of Triple-Negative Breast Cancer-Brain Metastasis. Cancers (Basel). 2022 Dec 19;14(24):6258. doi: 10.3390/cancers14246258. PMID: 36551742; PMCID: PMC9777321). The BRI of an agent for enhancing cell therapy includes any compounds that assists any cell therapy, including diluents, carriers, and excipients that facilitate the administration of compositions used in cell therapy such as water or other natural carriers and excipients.
It is noted the immunotherapeutic agents Anti-PD-1 antibody, CTLA-4 antibody, and PD-L1 antibody are all laboratory made monoclonal antibodies, and thus are not naturally occurring co-drugs. Applicant may consider amending claim 3 to limit the co-drug to these forms.
Claim 25 recites the oral pharmaceutical composition further comprises a pharmaceutically acceptable carrier, and the carrier comprises one or more of a diluent, dispersing agent, excipient, stabilizer, lubricant, and/or disintegrating agent. The BRI of the terms pharmaceutically acceptable carrier, diluent, dispersing agent, excipient, stabilizer, lubricant, and/or disintegrating agent includes many natural chemical compounds, including water.
Claim 26 recites that at least 50% of the bacteria in the oral pharmaceutical composition are viable bacteria. As established above, Lachnospiraceae are naturally occurring bacteria, and retain their natural status regardless of whether they are viable or not.
Claim 27 recites the composition is in the form of powder, microencapsulated powder, capsule, tablet, lozenge, granule, emulsion, suspension, suppository, beverage, food, pharmaceutical or nutritional product, food additive, dietary supplement, or dairy product. Powders, microencapsulated powders, capsules, granules, suspensions, beverages, foods, pharmaceutical or nutritional products, food additives, and dairy products include naturally occurring forms of the composition. Powders, microencapsulated powders, and granules can be brought about by natural desiccation processes or conditions. The BRI of the term capsules includes naturally occurring protective layers that surround cell walls of the Lachnospiraciae bacteria. The BRI of beverages includes naturally occurring juices or water. The BRI of foods and nutritional products includes foods that are comprised of naturally occurring material, such as lettuce, meats, etc. The BRI of pharmaceutical products and food additives includes just the oral composition itself. The BRI of dairy products includes naturally occurring milk.
It is noted that tablets, lozenges, emulsions, suppositories, and dietary supplements are non-natural forms of the composition, so Applicant may consider amending claim 3 to limit the composition to these forms in order to overcome the 35 USC §101 rejection.
Therefore, the instant invention recites a judicial exception of a product of nature (Step 2A Prong One: Yes).
This judicial exception is not integrated into a practical application and do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims are drawn to a composition of matter. The claims do not recite method steps which require the use of the product of nature for any specific purpose or therapeutic treatment. No additional elements are recited which are not otherwise discussed above.
Therefore, the instant invention is directed to the judicial exception of a product of nature and does not include any additional elements that amount to significantly more than the recited judicial exception of a product of nature, and so the instant invention is not patent eligible subject matter under 35 USC §101 (Step 2A Prong Two: No and Step 2B: No).
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.
Claims 3-4 and 23-27 are rejected under 35 U.S.C. 103 as being unpatentable over Ting et al. (US 20220054561 A1, effectively filed 14 December 2018) in view of Li et al. (Symbiotic gut microbes modulate human metabolic phenotypes. Proc Natl Acad Sci U S A. 2008 Feb 12;105(6):2117-22. doi: 10.1073/pnas.0712038105. Epub 2008 Feb 5. PMID: 18252821; PMCID: PMC2538887).
Regarding claims 3-4 and 23, Ting teaches a composition comprising Lachnospiraceae microbial strains (Ting Title), as an adjuvant to anti-cancer radiation therapy and/or anti-cancer chemotherapy (Ting Claims 34-37), which can be encapsulated into an enteric capsule [0048] and administered orally [0050].
Ting does not teach the Lachnospiraceae has a 16S rRNA with the nucleotide sequence of SEQ ID No. 1, or with at least 95% identity to the nucleotide sequence, or that the Lachnospiraceae comprises Lachnospiraceae sp. MNH 46686 with a deposit number of GDMCC No: 62002.
Li teaches a Lachnospiraceae strain comprising a 16s rRNA sequence that is 98.1% identical to the instant SEQ ID NO: 1 (Li clone SJTU_D_01_61, see alignment in Office Action Appendix). Li also teaches that the Lachnospiraceae strain was isolated from a human fecal sample, meaning the strain was a member of the human’s gut microbiota (Li pg. 2121 Materials and Methods para. 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 modify Ting’s orally administered composition comprising a Lachnospiraceae microbial strain to comprise Li’s Lachnospiraceae strain comprising a 16s rRNA sequence that is 98.1% identical to SEQ ID NO: 1 because one of ordinary skill in the art would recognize that Li’s Lachnospiraceae microbial strain would be an acceptable strain of Lachnospiraceae within Ting’s composition. Ting does not teach a specific strain of Lachnospiraceae to be used within their composition, nor does Ting suggest that the benefits of their composition would be limited to one specific strain of Lachnospiraceae. However, Ting does teach that their Lachnospiraceae is a member of the human microbiota, which correlates with Li’s teaching that their Lachnospiraceae strains are members of the human gut microbiota, so one of ordinary skill in the art would readily conclude that Li’s Lachnospiraceae strain would be compatible within Ting’s composition since Ting’s and Li’s Lachnospiraceae microbial strains are recognized equivalents of one another.
Regarding claim 24, the specification does not recite any specific definition for the term “an agent for enhancing cell therapy”, thus the broadest reasonable interpretation of the term is an agent for enhancing cell therapy includes any compounds that assists any cell therapy, including diluents, carriers, dispersing agents, and excipients that facilitate the administration of compositions used in cell therapy such as water or other natural carriers and excipients. Ting teaches the oral composition includes standard carriers such as mannitol, lactose, starch, magnesium stearate, polyvinyl pyrollidone, sodium saccharine, cellulose, magnesium carbonate, and an agent which controls release of the compound, thereby providing a timed or sustained release compound (Ting [68]-[69]).
Regarding claim 25, Ting teaches that the pharmaceutically acceptable carriers can include aqueous or non-aqueous solutions, disintegrants, diluents, granulating agents, lubricants, and binders (Ting [62]).
Regarding claim 26, Ting does not explicitly teach that at least 50% of the Lachnospiraceae bacteria are viable in the composition. Ting does teach that the Lachnospiraceae bacteria are able to colonize the intestine and must do so to provide their beneficial effect of surviving radiation treatment, indicating that the bacteria within the composition are living and viable (Ting [0095]). It would have been obvious to one of ordinary skill in the art to optimize the amount of viable Lachnospiraceae bacteria in the composition in order to ensure that the composition would provide the beneficial effect of surviving radiation treatment as Ting teaches. See MPEP §2144.05(II)(B).
Regarding claim 27, Ting teaches that the oral composition may be formulated as a liquid solution, suspension, emulsion, tablet, pill, capsule, sustained release formulation, powder, or suppository (Ting [0066]-[0067]).
Conclusion
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached on (571)-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/Alexander M Duryee/Examiner, Art Unit 1657
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