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
Claims 1-20 are pending.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 07/19/2024, 08/14/2024, 11/19/2024, 01/15/2025, and 01/12/2026 are acknowledged and have been considered.
Election/Restrictions
Applicant’s election without traverse of species Clostridium butyricum in the reply filed on 03/02/2026 is acknowledged.
Claim 7 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - This application fails to comply with the requirements of 37 CFR 1.831-1.834 because it does not contain a “Sequence Listing XML” as a separate part of the disclosure. A “Sequence Listing XML” is required because the claims recite 16S rRNA sequences of Akkermansia muciniphila, Clostridium butyricum, Anerobutyricum hallii, Clostridium beijerinckii and Bifidobacterium infantis. However, Applicant did not file any sequence listing.
Required response - Applicant must provide:
• A “Sequence Listing XML” part of the disclosure, as described above in item 1. or 2.; together with
o A statement that indicates the basis for the amendment, with specific references to particular parts of the application as originally filed, as required by 37 CFR 1.835(a)(3);
o A statement that the “Sequence Listing XML” includes no new matter as required by 37 CFR 1.835(a)(4)
AND
• A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph as required by 37 CFR 1.835(a)(2), consisting of:
o A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
o A copy of the amended specification without markings (clean version); and
o A statement that the substitute specification contains no new matter.
Claim Objections
Claims 4-6 and 8-20 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, claims 4-6 and 8-20 have not been further treated on the merits.
In claim 15, “in type” should be replaced by “is type”. Appropriate correction is required.
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 1-2 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 claims contain 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.
The instant claims 1-2 require a bacterial strain to increase UDCA levels in a subject selected from the group consisting of a bacterial strain comprising a 16S rRNA having 95% or greater sequence identity to a 16S rRNA sequence of Akkermansia muciniphila; a bacterial strain comprising a 16S rRNA having 95% or greater sequence identity to a 16S rRNA sequence of Clostridium butyricum; a bacterial strain comprising a 16S rRNA having 95% or greater sequence identity to a 16S rRNA sequence of Anerobutyricum hallii; a bacterial strain comprising a 16S rRNA having 95% or greater sequence identity to a 16S rRNA sequence of Clostridium beijerinckii; or a bacterial strain comprising a 16S rRNA having 95% or greater sequence identity to a 16S rRNA sequence of Bifidobacterium infantis.
The specification discloses two compositions: WBF-010 comprising Clostridium butyricum, Clostridium beijerinckii, and Bifidobacterium infantis; and WBF-011 comprising Clostridium butyricum, Clostridium beijerinckii, Bifidobacterium infantis, Akkermansia muciniphila, and Anerobutyricum hallii ([307], FIG. 1), and discloses that the plasma ursodeoxycholate increased among the bile acids potentially due to the activity of C. butyricum (Example 2, FIG. 3d and 3e). Applicant discloses increasing UDCA levels in the mammalian subject results in antagonizing the FXR receptor in the mammalian subject (page 52 lines 11-12). The specification provides insufficient written description to support the genus of bacteria encompassed by the claims. Due to the extremely broad nature of the encompassed bacteria, there is no description of a representative number of bacteria which have the required function of increasing the levels of UDCA in a subject.
Prior art Edgar (Bioinformatics 34.14 (2018): 2371-2375) reports that an optimal identity threshold of 99% for full-length sequence of 16s rRNA indicates same species (Abstract) and prior art Johnson (Nature communications 10.1 (2019): 5029) reports that 16s rRNA sequences of > 95% identity represent the same genus (Abstract). Thus, the claims are analyzed as encompassing any bacterial strain of the Akkermansiaceae family; any bacterial strain of the Clostridiaceae family; any bacterial strain of the Lachnospiracea family; any bacterial strain of the Bifidobacteriaceae family. Prior art Seo (Digestive diseases and sciences 58.12 (2013): 3534-3544) teaches Clostridium butyricum increases the level of UDCA in a subject (Table 4).
The prior art disclosure of a single species has not established a strong correlation between structure and function, such minimal disclosure in prior art would not lead one skilled in the art to be able to predict with a reasonable degree of confidence the structure of the claimed invention from a recitation of its function. Without such a correlation, the capability to recognize or understand the structure from the mere recitation of function is highly unlikely. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. The Clostridium butyricum strain described in Seo reference is not representative of the entire genus when there is substantial variation within the bacterial genus. There may be unpredictability in the functional results obtained from species other than those specifically disclosed in Seo reference. One of skill in the art would not have recognized that the inventor was in possession of the necessary common attributes or features possessed by the species of the genus in view of the single species disclosed by Seo.
For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. Therefore, the inventor was not in possession of the full genus of a bacterial strain to increase UDCA levels in a subject selected from the group consisting of a bacterial strain comprising a 16S rRNA having 95% or greater sequence identity to a 16S rRNA sequence of Akkermansia muciniphila; a bacterial strain comprising a 16S rRNA having 95% or greater sequence identity to a 16S rRNA sequence of Clostridium butyricum; a bacterial strain comprising a 16S rRNA having 95% or greater sequence identity to a 16S rRNA sequence of Anerobutyricum hallii; a bacterial strain comprising a 16S rRNA having 95% or greater sequence identity to a 16S rRNA sequence of Clostridium beijerinckii; or a bacterial strain comprising a 16S rRNA having 95% or greater sequence identity to a 16S rRNA sequence of Bifidobacterium infantis.
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 1-3 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.
Claims 1-2 recite a limitation of 95% or greater sequence identity to a 16S rRNA sequence of Akkermansia muciniphila, Clostridium butyricum, anerobutyricum hallii, Clostridium beijerinckii, and/or Bifidobacterium infantis but the claims do not recite a sequence identifier for each recited 16S rRNA sequence. The claims are indefinite because the 16S rRNA sequences do not have a defined structure or specific SEQ IDs.
Claim 3, which depends from claims 1-2, does not cure the indefiniteness and is also rejected.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
For the purpose of applying prior art, a bacterial strain with more than 95% sequence identity to a 16S rRNA of Clostridium butyricum is interpreted as reading on the Clostridium genus, and at least 99% sequence identity is interpreted as reading on the species of Clostridium butyricum. Thus, bacteria belonging to the Clostridium genus will read on the claims since that meets the 16s rRNA thresholds taught in the art, as discussed above.
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Seo (Digestive diseases and sciences 58.12 (2013): 3534-3544).
Regarding claims 1-3, Seo teaches orally administering to rats a composition with 9x107 cfu/g of Clostridium butyricum and teaches an increase in ursodeoxycholic acid levels (UDCA) in the rats (Abstract, Table 4, page 3535 right column first para.). Applicant discloses increasing UDCA levels in the mammalian subject results in antagonizing the FXR receptor in the mammalian subject (page 52 lines 11-12). Thus, the limitation “antagonizing farnesoid X receptor (FXR) in a mammalian subject” will be present when the teachings of Seo are practiced.
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Eid (WO 2020/068827 A1, published 04/02/2020).
Regarding claims 1-3, Eid teaches orally administering to a human subject having type 2 diabetes a composition comprising Clostridium beijerinckii, Clostridium butyricum, Bifidobacterium infantis, Akkermansia muciniphila, Eubacterium hallii, and inulin (Table 3, [0268]) and teaches administering 3.34x108 CFU/day of Clostridium butyricum (Table 3). Eid does not teach the composition increases ursodeoxycholic acid (UDCA) levels in the human subject.
However, Applicant discloses that a dose of 108 or greater CFUs of Clostridium butyricum is an amount effective to increase UDCA levels in the mammalian subject (See claim 8). Applicant discloses increasing UDCA levels in the mammalian subject results in antagonizing the FXR receptor in the mammalian subject (page 52 lines 11-12). MPEP 2111.02(II) states that if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Since Eid teaches the active method step, the population, and the dose, then the limitations of “increasing ursodeoxycholic acid (UDCA) levels in a mammalian subject” and “antagonizing farnesoid X receptor (FXR) in a mammalian subject” will be present when the teachings of Eid are practiced.
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Perraudeau (BMJ open diabetes research & care 8.1 (2020).
Regarding claims 1-3, Perraudeau teaches administering to a human with Type 2 diabetes the WBF-011 composition which contains inulin, Akkermansia muciniphila, Clostridium beijerinckii, Clostridium butyricum, Bifidobacterium infantis and Anaerobutyricum hallii (Abstract). Perraudeau does not teach the composition increases ursodeoxycholic acid (UDCA) levels in the human subject.
However, Applicant discloses that WBF-011 composition comprises 3x109 CFU of Clostridium butyricum (FIG. 1e) and discloses 108 or greater CFUs of Clostridium butyricum is an amount effective to increase UDCA levels in the mammalian subject (See claim 8). Applicant discloses increasing UDCA levels in the mammalian subject results in antagonizing the FXR receptor in the mammalian subject (page 52 lines 11-12). MPEP 2111.02(II) states that if the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Since Perraudeau teaches the active method step, the population, and the dose, then the limitations of “increasing ursodeoxycholic acid (UDCA) levels in a mammalian subject” and “antagonizing farnesoid X receptor (FXR) in a mammalian subject” will be present when the teachings of Perraudeau are practiced.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 10 of U.S. Patent No. 10,842,831 in view of Seo. Regarding claims 1-3, patent claim 1 recites a method of producing a microbial composition suitable for human consumption, the method comprising: (a) culturing Akkermansia muciniphila. Patent claim 10 recites the unit dosage form further comprises one or more of: Clostridium beijerinckii, Clostridium butyricum, Clostridium indolis, Bifidobacterium infantis.
Patent claims 1 and 10 do not recite increasing UDCA levels or antagonizing farnesoid X receptor.
However, Seo teaches orally administering to rats 9x107 cfu/g composition comprising Clostridium butyricum and teaches an increase in ursodeoxycholic acid levels (UDSA) in the rats (Abstract, Table 4, page 3535 right column first para.). Applicant discloses increasing UDCA levels in the mammalian subject results in antagonizing the FXR receptor in the mammalian subject (page 52 lines 11-12). Thus, the limitation “antagonizing farnesoid X receptor (FXR) in a mammalian subject” will be present when the teachings of Seo are practiced.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition recited in patent claims 1 and 10 by administering the composition with 9x107 cfu/g of Clostridium butyricum, as suggested by Seo. One of ordinary skill in the art would be motivated to do so in order to increase UDCA levels in the subject and treat liver disease.
Claims 1-3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 7, 11, 20-21, 23, 26 and 30 of U.S. Patent No. 10,668,116 in view of Seo.
Regarding claims 1-3, patent claims 1 and 20 recite a composition comprising Clostridium beijerinckii, Akkermansia muciniphila, Clostridium butyricum, Eubacterium
hallii, and an enteric coating. Patent claims 2 and 21 recite composition is suitable for oral delivery to a subject. Patent claims 4 and 23 recite composition is suitable for administration to a human subject. Patent claims 7 and 26 recite prebiotic comprises inulin. Patent claims 11 and 30 recite composition comprises at least about 107 colony forming units (CFU) of each of said Clostridium beijerinckii, said Akkermansia muciniphila, said Clostridium butyricum, and said Eubacterium hallii.
Patent claims 1-2, 4, 7, 11, 20-21, 23, 26 and 30 do not recite increasing UDCA levels or antagonizing farnesoid X receptor.
However, Seo teaches orally administering to rats 9x107 cfu/g composition comprising Clostridium butyricum and teaches an increase in ursodeoxycholic acid levels (UDSA) in the rats (Abstract, Table 4, page 3535 right column first para.). Applicant discloses increasing UDCA levels in the mammalian subject results in antagonizing the FXR receptor in the mammalian subject (page 52 lines 11-12). Thus, the limitation “antagonizing farnesoid X receptor (FXR) in a mammalian subject” will be present when the teachings of Seo are practiced.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition recited in patent claims 1-2, 4, 7, 11, 20-21, 23, 26 and 30 by administering the composition with 9x107 cfu/g of Clostridium butyricum, as suggested by Seo. One of ordinary skill in the art would be motivated to do so in order to increase UDCA levels in the subject and treat liver disease.
Claims 1-3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 7, and 14 of U.S. Patent No. 11,278,580 in view of Seo.
Regarding claims 1-3, patent claim 1 recites a composition comprising Akkermansia muciniphila. Patent claim 2 recites the composition is of an oral dosage form. Patent claim 7 recites the prebiotic is selected from the group consisting of an amino acid, a peptide, biotin, polydextrose, a fructooligosaccharide (FOS), a galactooligosaccharide (GOS), a mannan oligosaccharide (MOS), a xylooligosaccharide (XOS), inulin, lignin, psyllium, chitin, chitosan, a gum, high amylase cornstarch (HAS), a β-glucan, lactulose, oligofructose-enriched inulin oligofructose, oligodextrose, tagatose, trans-galactooligosaccharide, pectin, and a combination thereof. Patent claim 14 recites the composition further comprising at least one microbe comprising an rRNA sequence with at least about 97% sequence identity to an rRNA sequence from a microbe selected from the group consisting Anaerostipes caccae, Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium in/antis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum, Clostridium aminophilum, Clostridium beijerinckii, Clostridium butyricum, Clostridium colinum, Clostridium indolis, Clostridium orbiscindens, Enterococcus faecium, Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus, Oscillospira guilliermondii, Roseburia cecicola, Roseburia inulinivorans, Ruminococcus jlavefaciens, Ruminococcus gnavus, Ruminococcus obeum, Streptococcus cremoris, Streptococcus faecium, Streptococcus infantis, Streptococcus mutans, Streptococcus thermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus, Anaerotruncus colihominis, Clostridium sporogenes, Clostridium tetani, Coprococcus eutactus, Eubacterium cylindroides, Eubacterium dolichum, Eubacterium ventriosum, Roseburia faeccis, Roseburia hominis, Roseburia intestinalis, and any combination thereof.
Patent claims 1-2, 7, and 14 do not recite increasing UDCA levels or antagonizing farnesoid X receptor.
However, Seo teaches orally administering to rats 9x107 cfu/g composition comprising Clostridium butyricum and teaches an increase in ursodeoxycholic acid levels (UDSA) in the rats (Abstract, Table 4, page 3535 right column first para.). Applicant discloses increasing UDCA levels in the mammalian subject results in antagonizing the FXR receptor in the mammalian subject (page 52 lines 11-12). Thus the limitation “antagonizing farnesoid X receptor (FXR) in a mammalian subject” will be present when the teachings of Seo are practiced.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition recited in patent claims 1-2, 7, and 14 by administering the composition with 9x107 cfu/g of Clostridium butyricum, as suggested by Seo. One of ordinary skill in the art would be motivated to do so in order to increase UDCA levels in the subject and treat liver disease.
Claims 1-3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, and 10 of U.S. Patent No. 11,364,270 in view of Seo.
Regarding claims 1-3, patent claim 1 recites a method of producing a microbial composition suitable for human consumption, the method comprising: culturing Akkermansia muciniphila in a culture medium comprising substantially a plant-based culture medium, thereby generating cultured Akkermansia muciniphila; and formulating the cultured Akkermansia muciniphila into a unit dosage form thereby producing the microbial composition suitable for human consumption. Patent claim 6 recites the unit dosage form is a food composition in a form of a bar. Patent claim 10 recites the unit dosage form further comprises one or more of: Eubacterium hallii, Clostridium beijerinckii, Clostridium butyricum, Clostridium indolis, Bifidobacterium infantis, or Faecalibacterium prausnitzii.
Patent claims 1,6, and 10 do not recite increasing UDCA levels or antagonizing farnesoid X receptor.
However, Seo teaches orally administering to rats 9x107 cfu/g composition comprising Clostridium butyricum and teaches an increase in ursodeoxycholic acid levels (UDSA) in the rats (Abstract, Table 4, page 3535 right column first para.). Applicant discloses increasing UDCA levels in the mammalian subject results in antagonizing the FXR receptor in the mammalian subject (page 52 lines 11-12). Thus the limitation “antagonizing farnesoid X receptor (FXR) in a mammalian subject” will be present when the teachings of Seo are practiced.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition recited in patent claims 1, 6, and 10 by administering the composition with 9x107 cfu/g of Clostridium butyricum, as suggested by Seo. One of ordinary skill in the art would be motivated to do so in order to increase UDCA levels in the subject and treat liver disease.
Claims 1-3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 9, 12, and 14 of U.S. Patent No. 11,583,558 in view of Seo.
Regarding claims 1-3, patent claim 1 recites a method of treating a disorder in a subject with the disorder, the method comprising: administering a therapeutically effective amount of a microbial composition to the subject, wherein the microbial composition comprises two primary fermenter microbes and three secondary fermenter microbes that increase production of butyrate in the subject. Patent claim 6 recites the subject is human. Patent claim 9 recites the microbial composition is formulated for oral delivery. Patent claim 12 recites the prebiotic is inulin. Patent claim 14 recites the microbial composition comprises Akkermansia muciniphila as a primary fermenter, Bifidobacterium in/antis as a primary fermenter, Eubacterium hallii as a secondary fermenter, Clostridium beijerinckii as a secondary fermenter, and Clostridium
butyricum as a secondary fermenter.
Patent claims 1, 6, 9, 12, and 14 do not recite increasing UDCA levels or antagonizing farnesoid X receptor.
However, Seo teaches orally administering to rats 9x107 cfu/g composition comprising Clostridium butyricum and teaches an increase in ursodeoxycholic acid levels (UDSA) in the rats (Abstract, Table 4, page 3535 right column first para.). Applicant discloses increasing UDCA levels in the mammalian subject results in antagonizing the FXR receptor in the mammalian subject (page 52 lines 11-12). Thus, the limitation “antagonizing farnesoid X receptor (FXR) in a mammalian subject” will be present when the teachings of Seo are practiced.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition recited in patent claims 1, 6, 9, 12, and 14 by administering the composition with 9x107 cfu/g of Clostridium butyricum, as suggested by Seo. One of ordinary skill in the art would be motivated to do so in order to increase UDCA levels in the subject and treat liver disease.
Claims 1-3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 12, 13, and 20 of U.S. Patent No. 12,233,095 in view of Seo.
Regarding claims 1-3, patent claim 1 recites a method of treating hyperalgesia, anxiety, or both in a subject in need thereof, the method comprising: administering to the subject an effective amount of a microbial composition comprising a butyrate-producing microbe, wherein the butyrate-producing microbe
increases production of butyrate in the subject. Patent claim 7 recites the secondary fermenter is Clostridium beijerinckii, Clostridium butyricum, Clostridium indolis, Eubacterium hallii, Faecalibacterium prausnitzii, or any combination thereof. Patent claim 12 recites the prebiotic is inulin. Patent claim 13 recites the microbial composition
is formulated for oral delivery. Patent claim 20 recites the subject is human.
Patent claims 1, 7, 12-13, and 20 do not recite increasing UDCA levels or antagonizing farnesoid X receptor.
However, Seo teaches orally administering to rats 9x107 cfu/g composition comprising Clostridium butyricum and teaches an increase in ursodeoxycholic acid levels (UDSA) in the rats (Abstract, Table 4, page 3535 right column first para.). Applicant discloses increasing UDCA levels in the mammalian subject results in antagonizing the FXR receptor in the mammalian subject (page 52 lines 11-12). Thus the limitation “antagonizing farnesoid X receptor (FXR) in a mammalian subject” will be present when the teachings of Seo are practiced.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition recited in patent claims 1, 6, 9, 12, and 14 by administering the composition with 9x107 cfu/g of Clostridium butyricum, as suggested by Seo. One of ordinary skill in the art would be motivated to do so in order to increase UDCA levels in the subject and treat liver disease.
Claims 1-3 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5, and 9 of U.S. Patent No. 11,931,387 in view of Seo.
Regarding claims 1-3 and 10-11, patent claim 1 recites a composition comprising: a microbe comprising a 16S rRNA sequence that has at least 97% sequence identity to a 16S rRNA sequence of Akkermansia muciniphila, wherein the microbe is generated by growth on a plant based culture medium. Patent claim 2 recites the composition further comprises a second microbe comprising a 16S rRNA sequence that has at least about 95% sequence identity to a rRNA sequence of a microbe selected from the group consisting of: Anaerostipes caccae, Bifidobacterium adolescentis, Bifidobacterium bifidum, Bifidobacterium infantis, Bifidobacterium longum, Butyrivibrio fibrisolvens, Clostridium acetobutylicum, Clostridium aminophilum, Clostridium beijerinckii, Clostridium butyricum, Clostridium colinum, Clostridium indolis, Clostridium orbiscindens, Enterococcus faecium, Eubacterium hallii, Eubacterium rectale, Faecalibacterium prausnitzii, Fibrobacter succinogenes, Lactobacillus acidophilus, Lactobacillus brevis, Lactobacillus bulgaricus, Lactobacillus casei, Lactobacillus caucasicus, Lactobacillus fermentum, Lactobacillus helveticus, Lactobacillus lactis, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus rhamnosus Oscillospira guilliermondii, Roseburia cecicola, Roseb~ria inulinivorans, Ruminococcus flavefaciens, Ruminococcus gnavus, Ruminococcus obeum, Streptococcus cremoris, Streptococcus faecium, Streptococcus in/antis, Streptococcus mutans, Streptococcus thermophilus, Anaerofustis stercorihominis, Anaerostipes hadrus, Anaerotruncus colihomnis, Clostridium sporogenes, Clostridium tetani, Coprococcus eutactus, Eubacterium cylindroides, Eubacterium dolichum, Eubacterium ventriosum, Roseburiafaeccis, Roseburia hominis, Roseburia intestinalis, and any combination thereof. Patent claim 5 recites the composition further comprises Clostridium butyricum. Patent claim 9 recites the prebiotic is selected from the group consisting of: complex carbohydrates, complex sugars, resistant dextrins, resistant starch, amino acids, peptides, nutritional compounds, biotin, polydextrose, fructooligosaccharide (FOS), galactooligosaccharides (GOS), inulin, starch, lignin, psyllium, chitin, chitosan, gums, guar gum, high amylase cornstarch (HAS), cellulose, β-glucans, hemi-celluloses, lactulose, mannooligosaccharides, mannan oligosaccharides (MOS), oligofructose-enriched inulin, oligofructose, oligodextrose, tagatose, transgalactooligosaccharide, pectin, resistant starch, xylooligosaccharides (XOS), and any combination thereof.
Patent claims 1-2, 5, and 9 do not recite increasing UDCA levels or antagonizing farnesoid X receptor.
However, Seo teaches orally administering to rats 9x107 cfu/g composition comprising Clostridium butyricum and teaches an increase in ursodeoxycholic acid levels (UDSA) in the rats (Abstract, Table 4, page 3535 right column first para.). Applicant discloses increasing UDCA levels in the mammalian subject results in antagonizing the FXR receptor in the mammalian subject (page 52 lines 11-12). Thus, the limitation “antagonizing farnesoid X receptor (FXR) in a mammalian subject” will be present when the teachings of Seo are practiced.
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition recited in patent claims 1, 6, 9, 12, and 14 by administering the composition with 9x107 cfu/g of Clostridium butyricum, as suggested by Seo. One of ordinary skill in the art would be motivated to do so in order to increase UDCA levels in the subject and treat liver disease.
Conclusion
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/MARY A CRUM/Examiner, Art Unit 1657
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