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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 5, 7, 9-10, 12-14, 17, 19, and 23-25, and the species Anaerobutyricum hallii (claim 7), inulin (claim 13), and a capsule (claim 25) in the reply filed on 08/07/2026 is acknowledged.
Priority
The instant application filed on 09/13/2024 is a 371 of PCT/US2023/064462 filed on 03/15/2023 and claims priority to U.S. Provisional Application No. 63/320,000 filed on 03/15/2022. U.S. PRO 63/320,000 finds support for the instantly claimed invention; therefore, the effective filing date of the instant application is 03/15/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/16/2024, 11/19/2024, 01/15/2025, 01/12/2026, and 05/12/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The information disclosure statement filed 05/01/2025 fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered.
Claim Rejections - 35 USC § 112(a), Enablement
Claims 5, 7, 9-10, 12-14, 17, 19, and 23-25 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The invention appears to employ novel biological materials, specifically Akkermansia muciniphila strain PTCC Accession No. PTA-126838. Since the biological materials are essential to the claimed invention, they must be obtainable by a repeatable method set forth in the specification or otherwise readily available to the public. If the biological materials are not so obtainable or available, the requirements of 35 U.S.C. § 112 may be satisfied by a deposit of the biological materials.
If the deposit is made under the Budapest Treaty, then an affidavit or declaration by Applicant, or a statement by an attorney of record over his or her signature and registration number, stating that the specific biological materials have been deposited under the Budapest Treaty and that the biological materials will be irrevocably and without restriction or condition released to the public upon the issuance of a patent, would satisfy the deposit requirement made herein. If the deposit has not been made under the Budapest Treaty, then in order to certify that the deposit meets the criteria set forth in 37 C.F.R. § 1.801-1.809, Applicant may provide assurance of compliance by an affidavit or declaration, or by a statement by an attorney of record over his or her signature and registration number, showing that:
during the pendency of this application, access to the invention will be afforded to the Commissioner upon request;
all restrictions upon availability to the public will be irrevocably removed upon granting of the patent;
the deposit will be maintained in a public depository for a period of 30 years or 5 years after the last request or for the effective life of the patent, whichever is longer;
a test of the viability of the biological material at the time of deposit will be made (see 37 C.F.R. § 1.807); and
the deposit will be replaced if it should ever become inviable.
Applicant's attention is directed to M.P.E.P. § 2400 in general, and specifically to MPEP § 2411.05, as well as to 37 C.F.R. § 1.809(d), wherein it is set forth that "the specification shall contain the accession number for the deposit, the date of the deposit, the name and address of the depository, and a description of the deposited material sufficient to specifically identify it and to permit examination.” The specification should be amended to include this information; however, Applicant is cautioned to avoid the entry of new matter into the specification by adding any other information.
Claim Rejections - 35 USC § 102/103
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed 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.
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 5, 10, 17, 19, and 25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated, or in the alternative, under 35 U.S.C. 103 as being unpatentable over Seo (WO 2021/1040186; Date of Publication: March 4, 2021)
Seo’s general disclosure relates to “a novel Akkermansia muciniphila EB-AMDK27 strain having the effect of preventing or treating inflammatory disease or metabolic disease, and a pharmaceutical composition effective for preventing or treating inflammatory disease or metabolic disease, which contains the strain, a culture thereof, or a dried product thereof. While traditional probiotics generally have insufficient therapeutic effects on inflammatory or metabolic diseases, the disclosed next-generation probiotic strain has an excellent effect on the prevention or treatment of inflammatory disease and/or metabolic disease so that it may be used as a new prophylactic and therapeutic tool” (see, e.g., Seo, abstract).
Regarding claims 5, 10, 17, 19, and 25 pertaining to the Akkermansia muciniphila strain and composition, Seo teaches an Akkermansia muciniphila EB-AMDK27 strain for preventing or treating inflammatory disease or metabolic disease (see, e.g., Seo, [13]-[14]). Seo teaches that the Akkermansia muciniphila strain is freeze-dried (i.e., lyophilized) and can be formulated into a pharmaceutical composition (see, e.g., Seo, [60]-[61]). Seo teaches that the composition comprises viable Akkermansia muciniphila cells (see, e.g., Seo, [60]) and that the Akkermansia muciniphila composition can be formulated in the form of a capsule (see, e.g., Seo, [69]).
Claimed Akkermansia muciniphila PTA-126838
Genus, Species: Akkermansia muciniphila (see, e.g., instant specification, [0004])
Morphology: Gram-negative, non-motile (see, e.g., instant specification, [0002])
Growth: Strictly anaerobic (see, e.g., instant specification, [0002], [0034])
Intended use: Treatment of a metabolic disorder, such as insulin-resistance based disorders,
insulin sensitivity-based disorders, type-1 diabetes, type-2 diabetes, and obesity (see, e.g., instant specification, [0006])
Active state: Viable or non-viable, which can be lyophilized (see, e.g., instant specification,
[0043])
Dosage forms: Pill, capsule, lozenge, food bar, or gummy ball (see, e.g., instant specification,
[0016]).
Composition formulation: Pharmaceutical formulation, nutritional supplement, dietary
supplement, medical food (see, e.g., instant specification, [0014]).
Treatment results: Treatment of metabolic disorders such as insulin-resistance based
disorders, insulin-sensitivity based disorders, type-1-diabetes, type-2-
diabetes, and obesity (see, e.g., instant specification, [0006] & Example 3).
Prior Art Strain (Seo’s Akkermansia muciniphila EB-AMDK27)
Genus, Species: Akkermansia muciniphila (see, e.g., Seo, [13]).
Morphology: Gram-negative, non-motile (see, e.g., Seo, [48]).
Growth: Anaerobic growth conditions (see, e.g., Seo, [62]).
Intended use: Treating inflammatory disease or metabolic disease (see, e.g., Seo, [14]), and
suppression of appetite (see, e.g., Seo, [15]).
Active state: Viable (see, e.g., Seo, [60], [74]).
Dosage forms: Powder, granule, tablet, capsule or liquid (see, e.g., Seo, [69]).
Composition formulation: Pharmaceutical formulation and functional food compositions (see,
e.g., Seo, [15]-[16], [18]).
Treatment results: Therapeutic efficacy against both inflammatory disease and metabolic
disease, and thus can provide the remarkable effect of comprehensively
treating various diseases that are highly correlated with inflammation or
obesity (see, e.g., Seo, [52]).
The disclosure of Seo teaches the strain of Akkermansia muciniphila which appears to be identical to the presently claimed strain because they are structurally and functionally the same. Consequently, the claimed strain appears to be anticipated by the reference.
However, in the alternative, even if the reference strain and the claimed strain are not one and the same and there is in fact no anticipation (i.e., if Applicant proves some minor difference), the reference strain would, nevertheless, have rendered the claimed strain obvious for a substantially similar strain to one of ordinary skill in the art at the time the claimed invention was filed in view of the clearly close relationship between the strain’s properties/functions, growth characteristics, and intended use for treating metabolic diseases. Thus, the claimed invention was clearly prima facie obvious especially in the absence of sufficient, clear, and convincing evidence to the contrary.
Claim Rejections - 35 USC § 103, Obviousness
Claims 7 and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Seo as applied to claims 5, 10, 17, 19, and 25 above, and further in view of Kolterman (WO 2020/236979; Date of Publication: November 26, 2020) and Cheng (WO 2020/219442; Date of Publication: October 29, 2020), as evidenced by Shetty (Reclassification of Eubacterium hallii as Anaerobutyricum hallii gen. nov., comb. nov., and description of Anaerobutyricum soehngenii sp. nov., a butyrate and propionate-producing bacterium from infant faeces; 2018).
Seo’s general disclosure is discussed above.
However, Seo does not teach: the bacterial composition further comprising one or more additional microbes having a 16S rRNA sequence comprising at least 97% identity to the full length of a 16S rRNA sequence of Anaerobutyrcum hallii (claim 7); or wherein the composition is dairy-free (claim 23); or wherein the composition comprises substantially no animal products (claim 24).
Kolterman’s general disclosure relates to “microbial compositions that are selected to improve gut function in the subjects to which they are administered, so as to bring about treatment of liver disorders and/or the signs, symptoms and indicators of those disorders” (see, e.g., Kolterman, abstract). Moreover, Kolterman discloses that the microbial composition can comprise Akkermansia muciniphila (see, e.g., Kolterman, [0009]).
Regarding claim 7 pertaining to Anaerobutyrcum hallii, Kolterman teaches a microbial composition comprising two or more microbes, wherein one of the microbes can be Eubacterium hallii (see, e.g., Kolterman, [0009]), which has been reclassified as Anaerobutyricum hallii (see, e.g., Shetty, abstract). Additionally, Kolterman teaches the microbial population comprises an rRNA sequence comprising at least 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% sequence identity to an rRNA sequence of Eubacterium hallii (see, e.g., Kolterman, [0039]).
Regarding claims 23-24 pertaining to the composition, Kolterman teaches that the composition is completely free or substantially free of any products of animal origin or any dairy derived components (see, e.g., Kolterman, [0040]).
Cheng’s general disclosure relates to “methods and compositions comprising microbial populations with increased tolerability and improved shelf life” (see, e.g., Cheng, abstract).Regarding claim 23-24 pertaining to the composition being dairy free and substantially free of animal products, Cheng teaches an Akkermansia muciniphila compositions that is dairy free and animal product-free (see, e.g., Cheng, [00145]), wherein “a composition which is animal product-free or substantially animal product-free can be better tolerated by a subject having a health condition compared to a composition that contains animal products” (see, e.g., Cheng, [00146]) and “a composition which is dairy-free can be better tolerated in a lactose intolerant subject than is a composition that contains dairy-derived components. In such cases, a subject can experience, for example, less abdominal pain, gas, diarrhea, bloating, or other side effects when a dairy-free composition is administered than when a composition is administered that contains dairy-derived components” (see, e.g., Cheng, [00148]).
It would have been first obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce Seo’s Akkermansia muciniphila composition, wherein the composition further comprises Eubacterium hallii, which has been reclassified as Anaerobutyricum hallii, as taught by Kolterman. One would have been motivated to do so because Kolterman teaches that Eubacterium hallii has been shown to improve symptoms and indications of disorders that are associated with metabolic disorders, such as liver disorders and injuries (see, e.g., Kolterman, [0023]). Additionally, Kolterman teaches that Eubacterium hallii can be combined in a microbial composition with Akkermansia muciniphila for treatment of metabolic disorders (see, e.g., Kolterman, [0009], [0023], [0036]). Moreover, Seo teaches administration of an Akkermansia muciniphila strain to treat a metabolic disease (see, e.g., Seo, [12]). Therefore, based on the teachings of Seo and Kolterman, it would have been obvious to administer Akkermansia muciniphila composition, wherein the composition further comprises Eubacterium hallii, which has been reclassified as Anaerobutyricum hallii, because both bacteria can be used to treat metabolic disorders and 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 (see, e.g., MPEP 2144.06(I)). One would have expected success because Seo and Kolterman both teach administration of microbial compositions that comprise Akkermansia muciniphila in order to treat metabolic disorders.
It would have been secondly obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce Seo’s Akkermansia muciniphila composition, wherein the composition is completely free of any products of animal origin or any dairy derived components, as taught by Kolterman and Cheng. One would have been motivated to do so because Kolterman teaches that for compositions that are administered orally, the capsules, coatings, excipients, and other adjunct materials are free of “animal derived products, such as milk, milk proteins, animal derived gelatin, or other animal derived proteins” (see, e.g., Kolterman, [0073]). Additionally, Cheng teaches Akkermansia muciniphila compositions wherein “a composition which is animal product-free or substantially animal product-free can be better tolerated by a subject having a health condition compared to a composition that contains animal products” (see, e.g., Cheng, [00146]) and “a composition which is dairy-free can be better tolerated in a lactose intolerant subject than is a composition that contains dairy-derived components. In such cases, a subject can experience, for example, less abdominal pain, gas, diarrhea, bloating, or other side effects when a dairy-free composition is administered than when a composition is administered that contains dairy-derived components” (see, e.g., Cheng, [00148]). Moreover, Seo teaches an Akkermansia muciniphila EB-AMDK27 strain for preventing or treating inflammatory disease or metabolic disease (see, e.g., Seo, [13]-[14]), wherein the Akkermansia muciniphila composition can be formulated in the form of a capsule (see, e.g., Seo, [69]). Therefore, based on the teachings of Seo, Kolterman, and Cheng, it would have been obvious to produce an oral Akkermansia muciniphila composition that is dairy free and free of animal-derived components for the composition to be better tolerated by patients. One would have expected success because Seo, Kolterman, and Cheng all teach oral administration of microbial compositions that comprise Akkermansia muciniphila to treat disorders.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Seo, Kolterman and Cheng as applied to claims 5, 7, 10, 17, 19, and 23-25 above, and further in view of Mogna (WO 2020/212934; Date of Publication: October 22, 2020).
The references of Seo, Kolterman, and Cheng are discussed above.
However, the references do not teach: wherein the composition comprises at least 10^5 AFUs/g of each of the one or more additional microbes (claim 9).
Mogna’s general disclosure relates to “a cytofluorometric method applied to a biomass of freeze-dried bacterial cells (freeze-dried biomass), wherein said cytofluorometric method is for evaluating the stability of said freeze-dried bacterial cells. The present invention further regards a use of a cytofluorometry method applied to a method for the preparation of a freeze-dried biomass, and a use of a cytofluorometry method for evaluating the integrity of a cell wall present in freeze-dried bacterial cells” (see, e.g., Mogna, abstract).
Regarding claim 9 pertaining to AFUs/g of the microbes, Mogna teaches a freeze-dried bacterial composition comprising Eubacterium hallii (see, e.g., Mogna, pg. 6, line 20 & pg. 7, lines 6-7). Moreover, Mogna teaches samples with at least 1x105 AFUs/g (see, e.g., Mogna, Figure 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce an Akkermansia muciniphila composition further comprising Eubacterium hallii, which has been reclassified as Anaerobutyricum hallii, as taught by Seo and Kolterman, wherein the Eubacterium hallii (i.e., Anaerobutyricum hallii) is at least 1x105 AFUs/g, as taught by Mogna. One would have been motivated to do so because Mogna teaches that active fluorescent units (AFUs) are a physical/physiological parameter of cell integrity and viability (see, e.g., Mogna, pg. 5, lines 12-14). Additionally, Mogna teaches that using AFUs for lyophilized microbial cultures is better at determining the viability and stability of bacterial cells within the lyophilized cultures than colony forming units (CFUs) (see, e.g., Mogna, pg. 5, lines 5-9). Moreover, Seo, Kolterman, and Cheng all teach an Akkermansia muciniphila compositions wherein the Akkermansia muciniphila strain is freeze-dried (i.e., lyophilized) and comprises viable Akkermansia muciniphila cells (see, e.g., Seo, [60] & Kolterman, [0041], [0010] & Cheng, [0005]). One would have expected success because Seo, Kolterman, Cheng, and Mogna all teach microbial compositions comprising Akkermansia muciniphila for administration to patients.
Claims 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Seo as applied to claims 5, 10, 17, 19, and 25 above, and further in view of Cani (WO 2014/076246; Date of Publication: May 22, 2014).
Seo’s general disclosure is discussed above.
However, Seo does not teach: wherein the composition further comprises a prebiotic (claim 12); or wherein the prebiotic is inulin (claims 13-14).
Cani’s general disclosure relates to “Akkermansia muciniphila or fragments thereof for treating a metabolic disorder in a subject in need thereof” (see, e.g., Cani, abstract).
Regarding claims 12-14 pertaining to the composition comprising a prebiotic, Cani teaches that the pharmaceutical composition comprising Akkermansia muciniphila further comprises a prebiotic, wherein the prebiotic is inulin (see, e.g., Cani, pg. 21, line 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce Seo’s Akkermansia muciniphila composition, wherein the composition further comprises inulin, as taught by Cani. One would have been motivated to do so because Cani teaches that Akkermansia muciniphila is co-administered with a prebiotic to treat a metabolic disorder (see, e.g., Cani, pg. 5, lines 3-10). Additionally, Cani teaches “Akkermansia muciniphila abundance is decreased in obese and diabetic mice, whereas prebiotic treatment restores it to basal levels and improves metabolic endotoxemia and related disorders” (see, e.g., Cani, Figure 1), wherein the prebiotic is inulin (see, e.g., Cani, pg. 21, line 2). Moreover, Seo teaches administration of an Akkermansia muciniphila strain to treat a metabolic disease (see, e.g., Seo, [12]). Therefore, based on the teachings of Seo and Cani, it would have been obvious to include a prebiotic within the Akkermansia muciniphila composition to treat metabolic disorders and increase Akkermansia muciniphila basal levels. One would have expected success because Seo and Cani both teach Akkermansia muciniphila compositions for treatment of metabolic disorders.
Conclusion
Claims 5, 7, 9-10, 12-14, 17, 19, and 23-25 are rejected.
No claims are allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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