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
The preliminary amendment filed 03/30/2026 is entered. Claims 2, 11, 29-111 and 113-150 are canceled. Claims 1, 3-10, 12-28 and 112 are pending and under consideration.
The instant claims are entitled to an effective filing date of 09/16/2022.
Specification
Abstract: Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract filed 03/14/2025 recites “Methods and uses of compositions (e.g. comprising one or more microbial strains, one or more components, one or more metabolites, or a combination thereof) for treating insulin-associated diseases”, which is a repeat of information given in the title. See lines 1-2.
Claim Objections
Claims 4, 14 and 15 are objected to because of the following informalities:
Claim 4 recites “Polycystic” in line 6, which should be lowercased to “polycystic” because the term is in the middle of a sentence.
Claim 14 recite “Butyrylcamitine” in line 2, which is misspelled and should be replaced with “butyrylcarnitine”.
Claim 14 improperly capitalizes terms in the middle of a sentences. As such, the claim should be amended to recite “butyrylcarnitine, theobromine, p-hydroxyphenylpyruvic acid, propionic acid, picolinic acid, 2-hydroxy-4methylvaleric acid, N6-acetylysine, urocanic acid, N5-ethylglutamine, trigonelline, stachydrine, ectoine, 5-hydroxylysine, arginine (Arg), cholic acid, 2-(4-hydroxyphenyl)propionic acid, N-acetyltryptophan, hydroxyproline, argininosuccinic acid, glutamic acid (Glu), sarcosine, 5- methoxyindoleacetic acid, indole-3-lactic acid, isovalerylalanine, N-acetylleucine, 1- methylhistidine, N-acetylephenylalanine, proline (Pro)”.
Claim 15 improperly capitalizes terms in the middle of a sentences. As such, the claim should be amended to recite “4-hydroxyphenylpyruvic, ectoine, gramine, N-acetyl-L-phenylalanine, nepsilon-acetyl-L-lysine, stachydrine, trigonelline, 3-ureidopropionic acid, theobromine, hippuric acid, imidazolepropionic acid, NG-methyl-L-arginine, trans-urocanic Acid, N-acetyl-L-leucine, sarcosine, isobutyrylcarnitine, b-hydroxyisovaleric acid, L-theanine/N5-ethylglutamine, 5-hydroxylysine, phenaceturic acid, betaine, hydroxyproline, picolinic acid, 2-aminoadipic acid, glycerophosphocholine, carnitine, glycerol 3-phosphate, argininosuccinic acid, creatine, terephthalic acid, homocitrulline, mucic acid, homocysteinesulfinic acid, trimethyllysine, spermidine, glyoxylic acid, XA0013 C6H6O4S, 3-indoxylsulfuric acid, nicotinamide, N-formylglycine, ureidoglycolate, N-methylproline, glucaric acid, butyrylcarnitine, methionine sulfoxide, carboxymethyllysine, glycolic acid, phenaceturic acid, diethanolamine, phosphorylcholine, guanidinosuccinic acid, N-acetylhistidine, glyceric acid, S-methylmethionine, cysteine glutathione disulfide, kynurenine, N-acetylphenylalanine, threonic acid, malic acid, 7,8-dihydrobiopterin, homovanillic acid, taurocholic acid, 5-methoxyindoleacetic acid, butyrate, b-hydroxyisovaleric acid, 2-oxoglutaric acid, N-acetyltryptophan, thiaproline, hypotaurine, cholic acid, acetoacetic acid, ethanolamine, guanidoacetic acid, S-sulfocysteine, myristic acid C14:0 XA0027”
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1, 3-10, and 12-28 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.
The term “high” in claims 1 and 3 is a relative term which renders the claim indefinite. The term “high” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. As such, one of ordinary skill in the art cannot determine the distinction between a subject at risk of developing an insulin-associated disease, disorder or condition, compared to a subject at high risk of developing an insulin-associated disease, disorder or condition.
Claims 4-10, and 12-28 depend from claims 1 or 3 and are rejected for the reason set forth above.
Claim 15 is further indefinite because it recites “XA0013 C6H6O4S” in line 9 and “Myristic acid C14:0 XA0027” in the last line, which render the claim indefinite because it is unclear whether XA0013 C6H6O4S encompasses any C6H6O4S compound or a specific compound, and it is unclear whether Myristic acid C14:0 XA0027 encompasses any myristic acid or a specific compound.
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.
Claim 112 is rejected under 35 U.S.C. 101 because the claimed invention is directed to an abstract idea without significantly more. Each step described below is in reference to the subject matter eligibility test for products and processes (MPEP 2106).
Claim 112 recites “[a] method” in line 1, which is one of the statutory categories (Step 1: Yes).
Claim 112 also recites the process step of “determining whether the microbial strain affects levels of one or more features of the one or more pancreatic cells or pancreatic cell lines, wherein the one or more features are associated with the insulin-associated disease, disorder, or conditions”. According to the instant specification, determining refers to any form of measurement, and includes determining if an element is present or not. See [0051]. Therefore, “determining” is an act of evaluation that can practically be performed in the human mind. Accordingly, this step is an abstract idea categorized as a mental process judicial exception. (Step 2A Prong 1: Yes)
Besides the abstract idea, claim 112 requires adding a microbial strain to a culture comprising one or more pancreatic cells or one or more pancreatic cell lines that model an insulin-associated disease, disorder, or condition. This step is recited at a high level of generality such that the limitation encompasses adding any microbial strain to pancreatic cells that model any disease, disorder or condition associated with insulin. This provides insufficient specificity to add anything of significance to the judicial exception. Thus, at most, this additional step constitutes as a pre-solution activity because the purpose of the step is to gather data necessary for applying the abstract idea judicial exception. (Step 2A Prong 2: No)
The additional elements fail to amount to an inventive concept in view of the routine, well understood and conventional activities in the art. Halimi teaches adding bacterial cultures to pancreatic cells. See p. 9 left column last passage. The pancreatic cell lines include Capan-2 (ATCC® HTB-80™). See p. 9 first paragraph. As evidenced by ATCC, Capan-2 is from the pancreas of a patient with pancreatic adenocarcinoma. See p. 1 lines 3-4 after the Capan-2 header. As evidenced by Eibl, obesity and type-2 diabetes mellitus are risk factors for the development of pancreatic ductal adenocarcinoma. See p. 3 first passage last sentence thereof. As such, Halimi teaches adding a microbial strain to a culture comprising pancreatic cells that model an insulin-associated disease, disorder or condition. Thus, additional element in claim 112 does not amount to more than a recitation of the words “apply it” (or an equivalent) (Step 2B: No).
For all of these reasons, claim 112 is not patent eligible.
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.
Claims 1, 3-8, 16-18, 20-24, and 26-28 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Nandakumar (WO 2019/036510).
Regarding claims 1 and 3, Nandakumar teaches a method of treating a subject diagnosed with or at risk for a cholestatic disease or condition, the method comprising administering to the subject a microbial composition, wherein at least one bacterial OTU or species in the microbial composition can deconjugate a primary bile acid or bile salt. See claim 16 of Nandakumar. Examples of a cholestatic disease or condition include non-alcoholic fatty liver disease (i.e. insulin-associated disease). See p. 27 lines 28-30.
Regarding claim 4, Nandakumar teaches a subject diagnosed with or at risk for non-alcoholic fatty liver disease (i.e. insulin-associated disease). See claim 20 of Nandakumar.
Regarding claims 5-6, Nandakumar teaches a mammalian subject that is a human subject. See p. 28 line 20.
Regarding claim 7-8, Nandakumar teaches a microbial composition directly derived from human feces (i.e. a mammalian human microbiome). See claim 29 of Nandakumar.
Regarding claims 16-18, Nandakumar teaches formulations comprising OTUs or bacterial species from clade 297. See claim 10 of Nandakumar. Bifidobacterium breve in clade 297. See table 2, first row on p. 16.
Regarding claim 20, Nandakumar teaches a formulation comprising at least two different bacterial OTUs or species. See claim 4 of Nandakumar.
Regarding claim 21-22, Nandakumar teaches a formulation comprising at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 1 1 , 12, 13, 14, 1 5, 16, 1 7, 18, 1 9, 20, 21 , 22, 23, 24, 25, 26, 27, 28, 29, 30, 31 , 32, 33, 34, 35, 40, or 50 OTUs or bacterial species. See claim 6 of Nandakumar.
Regarding claim 23, Nandakumar teaches oral administration, and rectal administration. See p. 29 lines 32 and 34.
Regarding claim 24, Nandakumar teaches oral administration. See p. 29 line 32.
Regarding claim 26, Nandakumar teaches a formulation in the form of a syrup, liquid medium, tablet, capsule, powder, and gel-cap. See p. 26 lines 25-30.
Regarding claim 27-28, Nandakumar teaches a composition with a final titer 1.00E+07 (i.e. 1x107) CFU/strain for each dose, which overlaps with the. See p. 34 line 1.
Claims 1, 3-6, 16-19, and 23-26 are rejected under 35 U.S.C. 102(a)(1) or 102(a)(2) as being anticipated by Barrangou (US 2022/0213493, published July 7, 2022).
Regarding claims 1, 3 and 4, Barrangou teaches administering a therapeutic composition comprising an engineered bacterial cell. See claim 26 of Barrangou. The cell improves at least one physiological parameter associated with a disease or condition when administered to a subject in need. The disease or condition is selected from a group that includes nonalcoholic fatty liver disease, cardiovascular disease, obesity and diabetes. See [0011].
Regarding claims 5-6, Barrangou teaches the term “subject” including a mammal and a human. See [0071].
Regarding claims 16, Barrangou teaches a cell selected from a group that includes Bifidobacterium. See claim 10 of Barrangou. Barrangou teaches Clostridium butyricum, Bacillus subtilis, and Lactobacillus plantarum. See claim 11 of Barrangou.
Regarding claim 17, Barrangou teaches cell selected from a group that includes Bifidobacterium. See claim. 10 of Barrangou. Barrangou teaches cell selected from a group that includes Lactobacillus plantarum. See claim 11 of Barrangou.
Regarding claim 18, Barrangou teaches cell selected from a group that includes Lactobacillus plantarum. See claim 11 of Barrangou.
Regarding claim 19, Barrangou teaches the cell selected from a group that includes Bacillus subtilis. See claim 11 of Barrangou.
Regarding claim 23, Barrangou teaches administering genetically engineered
bacteria orally, and rectally. See [0093]. Barrangou teaches genetically engineered microorganism administered systemically, intravenously and intramuscularly. See [0094].
Regarding claim 24, Barrangou teaches administering the genetically engineered bacteria orally. See [0093].
Regarding claim 25, Barrangou teaches administering genetically engineered microorganism intravenously. See [0094].
Regarding claim 26, Barrangou teaches engineered bacteria formulated as syrup, liquid, tablet, gels, and capsules. See [0101].
Claims 3, 12 and 13 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kars (Diabetes, 2010, 59(8), 1899-1905).
Regarding claim 3, Kars teaches subjects that receive an oral treatment of tauroursodeoxycholic acid (TUDCA, i.e. a microbial metabolite). See p. 1900 intervention section first sentence. Kars teaches obese adult participants. See p. 1900 research design and methods first sentence.
Regarding claim 12, Kars discloses that TUDCA is a bile acid. See p. 1899 last full paragraph.
Regarding claim 13, Kars teaches tauroursodeoxycholic acid (TUDCA). See p. 1900 intervention section first sentence.
Claims 112 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Halimi (Gut Microbes, 2021, 13(1)), with evidence from ATCC (Capan-2 - HTB-80 | ATCC. (2020)) and Eibl (Journal of the Academy of Nutrition and Dietetics, 2018, 118(4), 555-567).
Claim interpretation: according to the instant specification, obesity and diabetes are insulin-associated diseases. See [0004]. Therefore, diseases associated with obesity and/or diabetes are also insulin-associated diseases.
Regarding claim 112, Halimi teaches bacterial cultures that are added to pancreatic cells. See p. 9 left column last passage. The pancreatic cell lines include Capan-2 (ATCC® HTB-80™). See p. 9 first paragraph. Halimi teaches examining pancreatic cell damage by measuring phosphorylated γH2A.X, a known hallmark of DNA double strand breakage and DNA damage response activation, and the extent of cell death after an overnight bacteria co-culture. See p. 4 left column last passage.
As evidenced by ATCC, Capan-2 is from the pancreas of a patient with pancreatic adenocarcinoma. See p. 1 lines 3-4 after the Capan-2 header.
As evidenced by Eibl, obesity and type-2 diabetes mellitus are risk factors for the development of pancreatic adenocarcinoma. See p. 3 first passage last sentence thereof.
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 1, 3-10 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Craven (Official journal of the American College of Gastroenterology, 2020, ACG, 115(7), 1055-1065).
Regarding claims 1 and 3, Craven teaches assigning patients with non-alcoholic fatty liver disease (i.e. insulin-associated disease) to autologous fecal microbiota transplants (FMT). See p. 1056 right column last full paragraph. Craven teaches collecting a baseline stool sample, and then delivering the autologous FMT to the duodenum. See p. 1057 first full paragraph. As shown in figure 7, the fecal microbiota composition at baseline of autologous FMT recipients includes microbial strains.
Craven does not explicitly teach administering to a subject a composition comprising one or more microbial strains or components; however, Craven indicates that the microbial strains present in the baseline fecal microbiota composition are present in the administered autologous FMT.
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to administer the autologous FMT to the subjects, as taught by Craven, and in the process administer one or more microbial strains.
Regarding claim 4, Craven teaches non-alcoholic fatty liver disease (i.e. insulin-associated disease). See p. 1056 right column last full paragraph.
Regarding claims 5-6, Craven teaches patients (i.e. human, mammals). See p. 1056 right column last full paragraph.
Regarding claim 7-8, Craven teaches the patients (i.e. human, mammal) fecal microbiome composition at baseline, before the autologous FMT. The fecal microbiota includes microbial strains. See figure 7.
Regarding claim 9, Craven teaches preparing FMT material from an autologous stool sample (i.e. a sample from the individual who will receive them), and delivering the autologous FMT. See p. 1057 first full paragraph.
Regarding claim 10, Craven teaches the fecal microbiota composition at baseline, 2, 7 days, 2, 6 weeks, 3, and 6 months post-FMT. See the caption of figure 7. As shown in figure 7, the fecal microbiota composition changes overtime. Craven suggests that FMT can alter (i.e. modulate) the microbiota composition. See p. 1056 left column paragraph 2.
Regarding claims 16-17, Craven discloses that the fecal microbiota composition of autologous FMT transplants at baseline include Coprococcus. See figure 7.
Claims 12, and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Nandakumar (WO 2019/036510).
The teachings of Nandakumar with respect to claims 1, 3-8, 16-18, 20-24, and 26-28 are discussed above and incorporated herein.
Regarding claim 12, Nandakumar teaches methods of treating a subject diagnosed with or at risk for a cholestatic disease or condition, the methods including administering to the subject UDCA (ursodeoxycholic acid) and a composition comprising bacteria. See claim 24 of Nandakumar. Nandakumar discloses that UDCA is an endogenous bile acid. See p. 30 lines 8-9. Furthermore, Nandakumar teaches a subject diagnosed with or at risk for non-alcoholic fatty liver disease (i.e. insulin-associated disease). See claim 20 of Nandakumar.
Nandakumar does not explicitly teach administering to a subject a composition comprising one or more metabolites that is or comprises a bile acid to a subject that has been diagnosed with or is at high risk of developing an insulin-associated disease, disorder, or condition.
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to administer the bile acid in a composition comprising bacteria to the subject diagnosed with or at risk of the insulin-associated disease based on Nandakumar’s own suggestion. One of ordinary skill in the art would have been motivated to do so because Nandakumar suggests that such composition is useful for treating non-alcoholic fatty liver disease (see p. 27 lines 27 and 30). There would have been a reasonable expectation of success because Nandakumar discloses that the UDCA can be administered as a separate composition or it can be combined with formulations (see p. 30 lines 12-13).
Regarding claims 14-15, Nandakumar teaches a cholic acid supplemented diet in example 2. See p. 40 lines 39-40. Furthermore, Nandakumar teaches a subject diagnosed with or at risk for non-alcoholic fatty liver disease (i.e. insulin-associated disease). See claim 20 of Nandakumar.
Although Nandakumar teaches cholic acid, Nandakumar does not explicitly teach administering the cholic acid to a subject that has been diagnosed with or is at high risk of developing an insulin-associated disease, disorder, or condition.
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to administer the cholic acid to the subject diagnosed with or at risk of the insulin-associated disease based on Nandakumar’s suggestion. One of ordinary skill in the art would have been motivated to do so because Nandakumar suggests that a cholic acid supplemented diet decreases CYP7A1 (i.e. a bile acid synthesizing enzyme) expression (see p.40 lines 39-40). There would have been a reasonable expectation of success because Nandakumar demonstrates cholic acid supplemented diet (see p. 40 lines 39-40).
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, 3-10, and 12-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6-10, 22-27, and 149-152 of copending Application No. 18/073,511 in view of Barrangou (US 2022/0213493, published July 7, 2022) and Nandakumar (WO 2019/036510).
Copending claim 1 recites a method of improving a Vagus nerve-associated disease, disorder, or condition, the method comprising: administering to a mammalian subject in need thereof a composition comprising microbial strains of Gluconacetobacter hansenii, Terrisporobacter glycolicus, Coprococcus catus, Lactobacillus plantarum, Veillonella atypica, and Bifidobacterium breve; wherein the Vagus nerve-associated disease, disorder, or condition is Amyotrophic lateral sclerosis (ALS).
Copending claim 6 recites the method of claim 1, wherein the mammalian subject is a human.
Copending claim 7 recites the method of claim 1, wherein the microbial strains are from a mammalian microbiome.
Copending claim 8 recites the method of claim 1, wherein the microbial strains are from a human microbiome.
Copending claim 9 recites the method of claim 8, wherein the mammalian subject is human and the microbiome is from the human subject.
Copending claim 10 recites the method of claim 9, wherein the microbiome is administered to maintain or modulate the microbiome of the human subject.
Copending claim 23 recites the method of claim 1, wherein the composition is administered topically, orally, subcutaneously, intravenously, intramuscularly, intracerebrally, intrathecally, rectally, opthalmically, intravitreally, or suprachoroidally.
Copending claim 24 recites the method of claim 1, wherein the composition is administered orally.
Copending claim 26 recites the method of claim 1, wherein the composition is formulated as a syrup, a liquid, a tablet, a troche, a gummy, a capsule, a powder, a gel, a film, an injection, or an eye drop.
Copending claim 27 recites the method of claim 1, wherein each microbial strain is present in the composition at a concentration from 101 to 1015 CFU.
Copending claim 149 recites the method of claim 1, wherein each microbial strain is present in the composition at a concentration of 106 CFU.
Copending claim 150 recites the method of claim 1, wherein the composition comprises ten or more microbial strains.
Copending claim 151 recites the method of claim 1, wherein the composition further comprises the microbial strains of Clostridium sp., Paenibacillus sp., Bacillus sp., and Acidaminococcus sp.
Copending claim 152 recites the method of claim 1, wherein the composition further comprises the microbial strains of Clostridium butyricum, Paenibacillus sp., Acidaminococcus sp., and Bacillus subtilis.
The copending claims lack: a subject that has been diagnosed with or at high risk of developing an insulin-associated disease, disorder, or condition (relevant to instant claims 1 and 3); the insulin-associated disease, disorder, or condition is or comprises diabetes, obesity, cardiovascular disease, non-alcoholic fatty liver disease, Wolfram syndrome, metabolic syndrome, insulin resistance, diabetic ketoacidosis, hyperosmolar hyperglycemic state, gestational diabetes, diabetic dermadromes, diabetic neuropathy, diabetic foot ulcers, maturity onset diabetes of the young, pancreatogenic diabetes, or Polycystic ovary syndrome (PCOS) (relevant to instant claim 4); wherein the one or more microbial metabolites is or comprises a bile acid (relevant to instant claim 12); wherein the one or more microbial metabolites is or comprises tauroursodeoxycholic acid (relevant to instant claim 13); wherein one or more microbial components or microbial metabolites is butyrylcamitine, theobromine, p-hydroxyphenylpyruvic acid, propionic acid, picolinic acid, 2-hydroxy-4methylvaleric acid, N6-acetylysine, urocanic acid, N5-ethylglutamine, trigonelline, stachydrine, ectoine, 5-hydroxylysine, Arg, cholic acid, 2-(4-hydroxyphenyl)propionic acid, N- acetyltryptophan, hydroxyproline, argininosuccinic acid, Glu, sarcosine, 5- methoxyindoleacetic acid, indole-3-lactic acid, isovalerylalanine, N-acetylleucine, 1- methylhistidine, N-acetylephenylalanine, Pro, or any combination thereof (relevant to instant claim 14); wherein one or more microbial components or microbial metabolites is 4-hydroxyphenylpyruvic, ectoine, gramine, N-acetyl-L-phenylalanine, nepsilon-acetyl-L-lysine, stachydrine, trigonelline, 3-ureidopropionic acid, theobromine, hippuric acid, imidazolepropionic acid, NG-methyl-L-arginine, trans-urocanic Acid, N-acetyl-L-leucine, sarcosine, isobutyrylcarnitine, b-hydroxyisovaleric acid, L-theanine/N5-ethylglutamine, 5-hydroxylysine, phenaceturic acid, betaine, hydroxyproline, picolinic acid, 2-aminoadipic acid, glycerophosphocholine, carnitine, glycerol 3-phosphate, argininosuccinic acid, creatine, terephthalic acid, homocitrulline, mucic acid, homocysteinesulfinic acid, trimethyllysine, spermidine, glyoxylic acid, XA0013 C6H6O4S, 3-indoxylsulfuric acid, nicotinamide, N-formylglycine, ureidoglycolate, N-methylproline, glucaric acid, butyrylcarnitine, methionine sulfoxide, carboxymethyllysine, glycolic acid, phenaceturic acid, diethanolamine, phosphorylcholine, guanidinosuccinic acid, N-acetylhistidine, glyceric acid, S-methylmethionine, cysteine glutathione disulfide, kynurenine, N-acetylphenylalanine, threonic acid, malic acid, 7,8-dihydrobiopterin, homovanillic acid, taurocholic acid, 5-methoxyindoleacetic acid, butyrate, b-hydroxyisovaleric acid, 2-oxoglutaric acid, N-acetyltryptophan, thiaproline, hypotaurine, cholic acid, acetoacetic acid, ethanolamine, guanidoacetic acid, S-sulfocysteine, myristic acid C14:0 XA0027 (relevant to instant claim 15).
However, Barrangou teaches a cell that improves at least one physiological parameter associated with a disease when administered to a subject in need thereof. See claim 13 of Barrangou. The disease is selected from a group that includes cardiovascular disease, obesity, diabetes and nonalcoholic fatty liver disease. Barrangou teaches the term “subject” to mean a mammal and a human. See [0071] (relevant to instant claims 1, 3 and 4). Nandakumar teaches administering to a subject ursodeoxycholic acid, i.e. a bile acid. See claim 24 of Nandakumar (relevant to instant claim 12). Barrangou teaches bile salt substrate including tauroursodeoxycholic acid (TUDCA). See claim 3 of Barrangou (relevant to instant claim 13). Nandakumar teaches a cholic acid supplemented diet. See p. 40 lines 39-40 (relevant to instant claims 14-15).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to substitute Barrangou’s subject in need of cardiovascular disease, obesity, diabetes and/or nonalcoholic fatty liver disease treatment for the mammalian subject recited in copending claim 1, and to further combine the composition recited in copending claim 1 with Nandakumar’s bile acid, Nandakumar’s cholic acid and Barrangou’s tauroursodeoxycholic acid in order to treat an insulin-associated disease.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-10, and 12-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-9, and 21-28 of copending Application No. 18/604,196 in view of Barrangou (US 2022/0213493, published July 7, 2022) and Nandakumar (WO 2019/036510).
Copending claim 1 recites a method of treating or preventing Alzheimer's Disease (AD), or Parkinson's Disease (PD), the method comprising: administering to a subject in need thereof a composition comprising microbial strains a Gluconacetobacter hansenii, Terrisporobacter glycolicus, Coprococcus catus, Lactobacillus plantarum, Veillonella atypica, and Bifidobacterium breve.
Copending claim 5 recites the method of claim 1, wherein the subject is a mammal.
Copending claim 6 recites the method of claim 1, wherein the subject is a human.
Copending claim 7 recites the method of claim 1, wherein the microbial strains are from a mammalian microbiome.
Copending claim 8 recites the method of claim 1, wherein the microbial strains are from a human microbiome.
Copending claim 9 recites the method of claim 8, wherein the human microbiome is the microbiome of the subject.
Copending claim 21 recites the method of claim 1, wherein the composition comprises at least seven microbial strains.
Copending claim 22 recites the method of claim 1, wherein the composition comprises at least ten microbial strains.
Copending claim 23 recites the method of claim 1, wherein the composition is administered topically, orally, subcutaneously, intravenously, intramuscularly, intracerebrally, intrathecally, rectally, opthalmically, intravitreally, or suprachoroidally.
Copending claim 24 recites the method of claim 1, wherein the composition is administered orally.
Copending claim 25 recites the method of claim 1, wherein the composition is administered intracerebrally.
Copending claim 26 recites the method of claim 1, wherein the composition is formulated as a syrup, a liquid, a tablet, a troche, a gummy, a capsule, a powder, a gel, a film, an injection, or an eye drop.
Copending claim 27 recites the method of claim 1, wherein each microbial strain is present in the composition at a concentration from 101 to 1015 CFU.
Copending claim 28 recites the method of claim 1, wherein each microbial strain is present in the composition at a concentration of at least 106 CFU.
Copending claim 149 recites the method of treating amyloid plaques or reducing plaque burden, plaque number, or plaque size in a subject diagnosed with Alzheimer's Disease (AD) or Parkinson's Disease (PD) the method comprising: administering to the subject in need thereof a composition comprising microbial strains a Gluconacetobacter hansenii, Terrisporobacter glycolicus, Coprococcus catus, Lactobacillus plantarum, Veillonella atypica, and Bifidobacterium breve.
The copending claims lack: a subject that has been diagnosed with or at high risk of developing an insulin-associated disease, disorder, or condition (relevant to instant claims 1 and 3); the insulin-associated disease, disorder, or condition is or comprises diabetes, obesity, cardiovascular disease, non-alcoholic fatty liver disease, Wolfram syndrome, metabolic syndrome, insulin resistance, diabetic ketoacidosis, hyperosmolar hyperglycemic state, gestational diabetes, diabetic dermadromes, diabetic neuropathy, diabetic foot ulcers, maturity onset diabetes of the young, pancreatogenic diabetes, or Polycystic ovary syndrome (PCOS) (relevant to instant claim 4); wherein the one or more microbial metabolites is or comprises a bile acid (relevant to instant claim 12); wherein the one or more microbial metabolites is or comprises tauroursodeoxycholic acid (relevant to instant claim 13); wherein one or more microbial components or microbial metabolites is butyrylcamitine, theobromine, p-hydroxyphenylpyruvic acid, propionic acid, picolinic acid, 2-hydroxy-4methylvaleric acid, N6-acetylysine, urocanic acid, N5-ethylglutamine, trigonelline, stachydrine, ectoine, 5-hydroxylysine, Arg, cholic acid, 2-(4-hydroxyphenyl)propionic acid, N- acetyltryptophan, hydroxyproline, argininosuccinic acid, Glu, sarcosine, 5- methoxyindoleacetic acid, indole-3-lactic acid, isovalerylalanine, N-acetylleucine, 1- methylhistidine, N-acetylephenylalanine, Pro, or any combination thereof (relevant to instant claim 14); wherein one or more microbial components or microbial metabolites is 4-hydroxyphenylpyruvic, ectoine, gramine, N-acetyl-L-phenylalanine, nepsilon-acetyl-L-lysine, stachydrine, trigonelline, 3-ureidopropionic acid, theobromine, hippuric acid, imidazolepropionic acid, NG-methyl-L-arginine, trans-urocanic Acid, N-acetyl-L-leucine, sarcosine, isobutyrylcarnitine, b-hydroxyisovaleric acid, L-theanine/N5-ethylglutamine, 5-hydroxylysine, phenaceturic acid, betaine, hydroxyproline, picolinic acid, 2-aminoadipic acid, glycerophosphocholine, carnitine, glycerol 3-phosphate, argininosuccinic acid, creatine, terephthalic acid, homocitrulline, mucic acid, homocysteinesulfinic acid, trimethyllysine, spermidine, glyoxylic acid, XA0013 C6H6O4S, 3-indoxylsulfuric acid, nicotinamide, N-formylglycine, ureidoglycolate, N-methylproline, glucaric acid, butyrylcarnitine, methionine sulfoxide, carboxymethyllysine, glycolic acid, phenaceturic acid, diethanolamine, phosphorylcholine, guanidinosuccinic acid, N-acetylhistidine, glyceric acid, S-methylmethionine, cysteine glutathione disulfide, kynurenine, N-acetylphenylalanine, threonic acid, malic acid, 7,8-dihydrobiopterin, homovanillic acid, taurocholic acid, 5-methoxyindoleacetic acid, butyrate, b-hydroxyisovaleric acid, 2-oxoglutaric acid, N-acetyltryptophan, thiaproline, hypotaurine, cholic acid, acetoacetic acid, ethanolamine, guanidoacetic acid, S-sulfocysteine, myristic acid C14:0 XA0027 (relevant to instant claim 15).
However, Barrangou teaches a cell that improves at least one physiological parameter associated with a disease when administered to a subject in need thereof. See claim 13 of Barrangou. The disease is selected from a group that includes cardiovascular disease, obesity, diabetes and nonalcoholic fatty liver disease (relevant to instant claims 1, 3 and 4). Nandakumar teaches administering to a subject ursodeoxycholic acid, i.e. a bile acid. See claim 24 of Nandakumar (relevant to instant claim 12). Barrangou teaches bile salt substrate including tauroursodeoxycholic acid (TUDCA). See claim 3 of Barrangou (relevant to instant claim 13). Nandakumar teaches a cholic acid supplemented diet. See p. 40 lines 39-40 (relevant to instant claims 14-15).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to substitute Barrangou’s subject in need of cardiovascular disease, obesity, diabetes and/or nonalcoholic fatty liver disease treatment for the subject recited in copending claim 1, and to further combine the composition recited in copending claim 1 with Nandakumar’s bile acid, Nandakumar’s cholic acid and Barrangou’s tauroursodeoxycholic acid in order to treat an insulin-associated disease.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-10, and 12-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-9, 11, 13, 19, and 22-24 of copending Application No. 18/244,685 in view of Barrangou (US 2022/0213493, published July 7, 2022) and Nandakumar (WO 2019/036510).
Copending claim 1 recites a method of treating an eye disorder, the method comprising: administering to a subject in need thereof a composition consisting of six to ten microbial strains, wherein the microbial strains comprise Gluconacetobacter hansenii, Terrisporobacter glycolicus, Coprococcus catus, Lactobacillus plantarum, Veillonella atypica, and Bifidobacterium breve, and wherein the eye disorder is Age-related Macular Degeneration (AMD).
Copending claim 5 recites the method of claim 1, wherein the subject is a mammal.
Copending claim 6 recites the method of claim 1, wherein the subject is a human.
Copending claim 7 recites the method of claim 1, wherein the microbial strains are from a mammalian microbiome.
Copending claim 8 recites the method of claim 1, wherein the microbial strains are from a human microbiome.
Copending claim 9 recites the method of claim 8, wherein the human microbiome is the microbiome of the subject.
Copending claim 13 recites the method of claim 1, wherein the composition further comprises Clostridium butyricum, Paenibacillus sp., Bacillus subtilis, and Acidaminococcus sp.
Copending claim 19 recites the method of claim 1, wherein the composition is administered topically, orally, opthalmically, intravitreally, or suprachoroidally.
Copending claim 22 recites the method of claim 1, wherein the composition is formulated as a syrup, a liquid, a tablet, a troche, a gummy, a capsule, a powder, a gel, a film, an injection, or an eye drop.
Copending claim 23 recites the method of claim 1, wherein each microbial strain of the composition is available at a concentration from 101 to 1015 CFU.
Copending claim 24 recites the method of claim 1, wherein each microbial strain of the composition is available at a concentration of at least 106 CFU.
The copending claims lack: a subject that has been diagnosed with or at high risk of developing an insulin-associated disease, disorder, or condition (relevant to instant claims 1 and 3); the insulin-associated disease, disorder, or condition is or comprises diabetes, obesity, cardiovascular disease, non-alcoholic fatty liver disease, Wolfram syndrome, metabolic syndrome, insulin resistance, diabetic ketoacidosis, hyperosmolar hyperglycemic state, gestational diabetes, diabetic dermadromes, diabetic neuropathy, diabetic foot ulcers, maturity onset diabetes of the young, pancreatogenic diabetes, or Polycystic ovary syndrome (PCOS) (relevant to instant claim 4); wherein the one or more microbial metabolites is or comprises a bile acid (relevant to instant claim 12); wherein the one or more microbial metabolites is or comprises tauroursodeoxycholic acid (relevant to instant claim 13); wherein one or more microbial components or microbial metabolites is butyrylcamitine, theobromine, p-hydroxyphenylpyruvic acid, propionic acid, picolinic acid, 2-hydroxy-4methylvaleric acid, N6-acetylysine, urocanic acid, N5-ethylglutamine, trigonelline, stachydrine, ectoine, 5-hydroxylysine, Arg, cholic acid, 2-(4-hydroxyphenyl)propionic acid, N- acetyltryptophan, hydroxyproline, argininosuccinic acid, Glu, sarcosine, 5- methoxyindoleacetic acid, indole-3-lactic acid, isovalerylalanine, N-acetylleucine, 1- methylhistidine, N-acetylephenylalanine, Pro, or any combination thereof (relevant to instant claim 14); wherein one or more microbial components or microbial metabolites is 4-hydroxyphenylpyruvic, ectoine, gramine, N-acetyl-L-phenylalanine, nepsilon-acetyl-L-lysine, stachydrine, trigonelline, 3-ureidopropionic acid, theobromine, hippuric acid, imidazolepropionic acid, NG-methyl-L-arginine, trans-urocanic Acid, N-acetyl-L-leucine, sarcosine, isobutyrylcarnitine, b-hydroxyisovaleric acid, L-theanine/N5-ethylglutamine, 5-hydroxylysine, phenaceturic acid, betaine, hydroxyproline, picolinic acid, 2-aminoadipic acid, glycerophosphocholine, carnitine, glycerol 3-phosphate, argininosuccinic acid, creatine, terephthalic acid, homocitrulline, mucic acid, homocysteinesulfinic acid, trimethyllysine, spermidine, glyoxylic acid, XA0013 C6H6O4S, 3-indoxylsulfuric acid, nicotinamide, N-formylglycine, ureidoglycolate, N-methylproline, glucaric acid, butyrylcarnitine, methionine sulfoxide, carboxymethyllysine, glycolic acid, phenaceturic acid, diethanolamine, phosphorylcholine, guanidinosuccinic acid, N-acetylhistidine, glyceric acid, S-methylmethionine, cysteine glutathione disulfide, kynurenine, N-acetylphenylalanine, threonic acid, malic acid, 7,8-dihydrobiopterin, homovanillic acid, taurocholic acid, 5-methoxyindoleacetic acid, butyrate, b-hydroxyisovaleric acid, 2-oxoglutaric acid, N-acetyltryptophan, thiaproline, hypotaurine, cholic acid, acetoacetic acid, ethanolamine, guanidoacetic acid, S-sulfocysteine, myristic acid C14:0 XA0027 (relevant to instant claim 15).
However, Barrangou teaches a cell that improves at least one physiological parameter associated with a disease when administered to a subject in need thereof. See claim 13 of Barrangou. The disease is selected from a group that includes cardiovascular disease, obesity, diabetes and nonalcoholic fatty liver disease (relevant to instant claims 1, 3 and 4). Barrangou teaches bile salt substrate selected from a group that includes TUDCA (i.e. Tauroursodeoxycholic acid, a bile acid). See claim 3 of Barrangou (relevant to instant claims 12-13). Barrangou teaches bacterial cells described capable of increasing the level of cholic acid (CA) in a subject or cell. See [0082] (relevant to instant claims 14-15). Nandakumar teaches administering to a subject ursodeoxycholic acid, i.e. a bile acid. See claim 24 of Nandakumar (relevant to instant claim 12). Barrangou teaches bile salt substrate including tauroursodeoxycholic acid (TUDCA). See claim 3 of Barrangou (relevant to instant claim 13). Nandakumar teaches a cholic acid supplemented diet. See p. 40 lines 39-40 (relevant to instant claims 14-15).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to substitute Barrangou’s subject in need of cardiovascular disease, obesity, diabetes and/or nonalcoholic fatty liver disease treatment for the subject recited in copending claim 1, and to further combine the composition recited in copending claim 1 with Nandakumar’s bile acid, Nandakumar’s cholic acid and Barrangou’s tauroursodeoxycholic acid in order to treat an insulin-associated disease.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-10, 12-28 and 112 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-8, and 12-29 of copending Application No. 18/935,074 in view of Barrangou (US 2022/0213493, published July 7, 2022), Nandakumar (WO 2019/036510), and Halimi (Gut Microbes, 2021, 13(1)), with evidence from ATCC (Capan-2 - HTB-80 | ATCC. (2020)) and Eibl (Journal of the Academy of Nutrition and Dietetics, 2018, 118(4), 555-567).
Copending claim 1 recites a method comprising:
determining a level of one or more metabolites in a sample from a subject, wherein the subject has received:
(i) a composition comprising ten or more microbial strains;
(ii) a composition comprising one or more lipopolysaccharides; or
(iii) a combination thereof.
Copending claim 2 recites the method of claim 1, wherein the subject is a mammal.
Copending claim 3 recites the method of claim 1, wherein the subject is a human.
Copending claim 4 recites the method of claim 1, wherein the ten or more microbial strains are from a mammalian microbiome.
Copending claim 5 recites the method of claim 1, wherein the ten or more microbial strains are from a human microbiome.
Copending claim 7 recites the method of claim 1, wherein the ten or more microbial strains are selected from TABLE 5.
Copending claim 8 recites the method of claim 1, wherein the ten or more microbial strains comprise are Gluconacetobacter hansenii, Terrisporobacter glycolicus, Coprococcus sp., Lactobacillus plantarum, Clostridium butyricum, Paenibacillus sp., Veillonella sp., Bifidobacterium sp., Bacillus subtilis, and Acidaminococcus sp.
Copending claim 12 recites the method of claim 1, wherein the composition comprises Gluconacetobacter hansenii, Terrisporobacter glycolicus, Coprococcus sp., Lactobacillus plantarum, Clostridium butyricum, Paenibacillus sp., Veillonella sp., Bifidobacterium sp., Bacillus subtilis, and Acidaminococcus sp.
Copending claim 16 recites the method of claim 1, wherein at least one of the one or more metabolites is associated with a disease, disorder, or condition.
Copending claim 17 recites the method of claim 16, wherein the subject is suffering from or at risk of suffering from the disease, disorder, or condition.
Copending claim 18 recites the method of claim 1, wherein the sample is or comprises a cell or tissue.
Copending claim 19 recites the method of claim 1, wherein the sample is or comprises a bodily fluid.
Copending claim 20 recites the method of claim 1, wherein the sample is or comprises amniotic fluid, aqueous humor, ascites, bile, bone marrow, blood, breast milk, cerebrospinal fluid, cerumen, chyle, chime, ejaculate, endolymph, exudate, feces, gastric acid, gastric juice, lymph, mucus, pericardial fluid, perilymph, peritoneal fluid, pleural fluid, pus, rheum, saliva, sebum, semen, serum, smegma, sputum, synovial fluid, sweat, tears, urine, vaginal secretions, vitreous humour, vomit, interstitial fluid, lymphatic fluid, plasma, mucous, digestive fluid, stool, and/or combinations or component(s) thereof.
Copending claim 21 recites the method of claim 1, wherein determining a level of one or more metabolites in a sample from the subject comprises quantifying the level of one or more metabolites in a sample from the subject.
Copending claim 22 recites the method of claim 1, further comprising administering to the subject the composition comprising ten or more microbial strains.
Copending claim 23 recites the method of claim 21, further comprising comparing the level of one or more metabolites in the sample from the subject to a reference value.
Copending claim 24 recites the method of claim 23, wherein the reference value is a control reference value.
Copending claim 25 recites the method of claim 23, wherein the reference value is a level of one or more metabolites in a control sample from the subject, wherein the control sample was obtained from the subject prior to the subject receiving the ten or more microbial strains, one or more lipopolysaccharides, or both.
Copending claim 26 recites the method of claim 1, wherein the method is a method of modulating one or more metabolites in the subject.
Copending claim 27 recites the method of claim 1, wherein the method is a method of characterizing the ability of ten more microbial strains to modulate one or more metabolites in the subject.
Copending claim 28 recites the method of claim 1, wherein the method is a method of characterizing the metabolome of the subject.
Copending claim 29 recites the method of claim 1, wherein the method is a method of treating or ameliorating a disease, disorder, or condition in the subject, wherein the disease, disorder, or condition is associated with one or more metabolites.
The copending claims lack: a subject that has been diagnosed with or at high risk of developing an insulin-associated disease, disorder, or condition (relevant to instant claims 1 and 3); the insulin-associated disease, disorder, or condition is or comprises diabetes, obesity, cardiovascular disease, non-alcoholic fatty liver disease, Wolfram syndrome, metabolic syndrome, insulin resistance, diabetic ketoacidosis, hyperosmolar hyperglycemic state, gestational diabetes, diabetic dermadromes, diabetic neuropathy, diabetic foot ulcers, maturity onset diabetes of the young, pancreatogenic diabetes, or Polycystic ovary syndrome (PCOS) (relevant to instant claim 4); wherein the one or more microbial metabolites is or comprises a bile acid (relevant to instant claim 12); wherein the one or more microbial metabolites is or comprises tauroursodeoxycholic acid (relevant to instant claim 13); wherein one or more microbial components or microbial metabolites is butyrylcamitine, theobromine, p-hydroxyphenylpyruvic acid, propionic acid, picolinic acid, 2-hydroxy-4methylvaleric acid, N6-acetylysine, urocanic acid, N5-ethylglutamine, trigonelline, stachydrine, ectoine, 5-hydroxylysine, Arg, cholic acid, 2-(4-hydroxyphenyl)propionic acid, N- acetyltryptophan, hydroxyproline, argininosuccinic acid, Glu, sarcosine, 5- methoxyindoleacetic acid, indole-3-lactic acid, isovalerylalanine, N-acetylleucine, 1- methylhistidine, N-acetylephenylalanine, Pro, or any combination thereof (relevant to instant claim 14); wherein one or more microbial components or microbial metabolites is 4-hydroxyphenylpyruvic, ectoine, gramine, N-acetyl-L-phenylalanine, nepsilon-acetyl-L-lysine, stachydrine, trigonelline, 3-ureidopropionic acid, theobromine, hippuric acid, imidazolepropionic acid, NG-methyl-L-arginine, trans-urocanic Acid, N-acetyl-L-leucine, sarcosine, isobutyrylcarnitine, b-hydroxyisovaleric acid, L-theanine/N5-ethylglutamine, 5-hydroxylysine, phenaceturic acid, betaine, hydroxyproline, picolinic acid, 2-aminoadipic acid, glycerophosphocholine, carnitine, glycerol 3-phosphate, argininosuccinic acid, creatine, terephthalic acid, homocitrulline, mucic acid, homocysteinesulfinic acid, trimethyllysine, spermidine, glyoxylic acid, XA0013 C6H6O4S, 3-indoxylsulfuric acid, nicotinamide, N-formylglycine, ureidoglycolate, N-methylproline, glucaric acid, butyrylcarnitine, methionine sulfoxide, carboxymethyllysine, glycolic acid, phenaceturic acid, diethanolamine, phosphorylcholine, guanidinosuccinic acid, N-acetylhistidine, glyceric acid, S-methylmethionine, cysteine glutathione disulfide, kynurenine, N-acetylphenylalanine, threonic acid, malic acid, 7,8-dihydrobiopterin, homovanillic acid, taurocholic acid, 5-methoxyindoleacetic acid, butyrate, b-hydroxyisovaleric acid, 2-oxoglutaric acid, N-acetyltryptophan, thiaproline, hypotaurine, cholic acid, acetoacetic acid, ethanolamine, guanidoacetic acid, S-sulfocysteine, myristic acid C14:0 XA0027 (relevant to instant claim 15); wherein the composition is administered topically, orally, subcutaneously, intravenously, intramuscularly, intracerebrally, intrathecally, rectally, opthalmically, intravitreally, or suprachoroidally (relevant to instant claim 23); administered orally (relevant to instant claim 24); administered intravenously (relevant to instant claim 25); wherein the composition is formulated as a syrup, a liquid, a tablet, a troche, a gummy, a capsule, a powder, a gel, a film, an injection, or an eye drop (relevant to instant claim 26); the one or more microbial strains is present in the composition at a concentration from 101 to 1015 CFU (relevant to instant claim 27); and the one or more microbial strains is present in the composition at a concentration of at least 106 CFU (relevant to instant claim 28).
However, Barrangou teaches a cell that improves at least one physiological parameter associated with a disease when administered to a subject in need thereof. See claim 13 of Barrangou. The disease is selected from a group that includes cardiovascular disease, obesity, diabetes and nonalcoholic fatty liver disease (relevant to instant claims 1, 3 and 4). Nandakumar teaches administering to a subject ursodeoxycholic acid, i.e. a bile acid. See claim 24 of Nandakumar (relevant to instant claim 12). Barrangou teaches bile salt substrate including tauroursodeoxycholic acid (TUDCA). See claim 3 of Barrangou (relevant to instant claim 13). Nandakumar teaches a cholic acid supplemented diet. See p. 40 lines 39-40 (relevant to instant claims 14-15). Barrangou teaches administering the genetically engineered bacteria orally [0093] or intravenously [0094] (relevant to instant claims 23-25). Nandakumar teaches a composition with a final titer 1.00E+07 (i.e. 1x107) CFU/strain for each dose, which overlaps with the. See p. 34 line 1 (relevant to instant claims 27-28).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to substitute Barrangou’s subject in need of cardiovascular disease, obesity, diabetes and/or nonalcoholic fatty liver disease treatment for the subject recited in copending claim 1; to further optimize the quantity of the one or more microbial strains recited in copending claim 1 based on Nandakumar’s 1x107 cfu/strain quantity; and to further combine the composition recited in copending claim 1 with Nandakumar’s bile acid, Nandakumar’s cholic acid and Barrangou’s tauroursodeoxycholic acid in order to treat an insulin-associated disease.
The copending claims lack: a method of characterizing a microbial strain, comprising: adding the microbial strain to a culture comprising one or more pancreatic cells or one or more pancreatic cell lines that model an insulin-associated disease, disorder, or condition, and determining whether the microbial strain affects levels of one or more features of the one or more pancreatic cells or pancreatic cell lines, wherein the one or more features are associated with the insulin-associated disease, disorder, or condition (relevant to instant claim 112).
However, Halimi teaches bacterial cultures that are added to pancreatic cells. See p. 9 left column last passage. The pancreatic cell lines include Capan-2. See p. 9 first paragraph. Halimi teaches examining pancreatic cell damage by measuring phosphorylated γH2A.X a known hallmark of DNA double strand- breakage and DNA damage response activation, and the extent of cell death after an overnight bacteria co-culture. See p. 4 left column last passage. As evidenced by ATCC, Capan-2 is from the pancreas of a patient with pancreatic adenocarcinoma. See p. 1 lines 3-4 after the Capan-2 header. As evidenced by Eibl, obesity and type-2 diabetes mellitus are risk factors for the development of pancreatic adenocarcinoma. See p. 3 first passage last sentence thereof.
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to substitute Halimi’s pancreatic cells for the sample recited in copending claim 1 and to further apply the co-culture step of Halimi in order to characterize a microbial strain.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-10, and 12-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11,957,723 in view of Barrangou (US 2022/0213493, published July 7, 2022) and Nandakumar (WO 2019/036510).
Patent claim 1 recites a method of treating or preventing amyotrophic lateral sclerosis, the method comprising:
administering to a subject in need thereof a composition comprising Gluconacetobacter hansenii, Terrisporobacter glycolicus, Coprococcus catus, Lactobacillus plantarum, Veillonella atypica, and Bifidobacterium breve.
Patent claim 2 recites the method of claim 1, wherein the subject is a mammal.
Patent claim 3 recites the method of claim 1, wherein the subject is a human.
Patent claim 4 recites the method of claim 1, wherein the composition comprises seven or more microbial strains.
Patent claim 5 recites the method of claim 1, wherein the composition comprises ten or more microbial strains.
Patent claim 6 recites the method of claim 1, wherein the composition is administered topically, orally, subcutaneously, intravenously, intramuscularly, intracerebrally, intrathecally, rectally, opthalmically, intravitreally, or suprachoroidally.
Patent claim 7 recites the method of claim 6, wherein the composition is administered orally.
Patent claim 9 recites the method of claim 1, wherein the composition is formulated as a syrup, a liquid, a tablet, a troche, a gummy, a capsule, a powder, a gel, a film, an injection, or an eye drop.
Patent claim 10 recites the method of claim 1, wherein each microbial strain is present in the composition at a concentration from 101 to 1015 CFU.
Patent claim 11 recites the method of claim 1, wherein each microbial strain is present in the composition at a concentration of at least 106 CFU.
Patent claim 12 recites the method of claim 1, wherein Gluconacetobacter hansenii, Terrisporobacter glycolicus, Coprococcus catus, Lactobacillus plantarum, Veillonella atypica, and Bifidobacterium breve are administered to modulate the microbiome of the subject.
Patent claim 13 recites the method of claim 1, wherein Gluconacetobacter hansenii, Terrisporobacter glycolicus, Coprococcus catus, Lactobacillus plantarum, Veillonella atypica, and Bifidobacterium breve are administered to maintain the microbiome of the subject.
The patent claims lack: a subject that has been diagnosed with or at high risk of developing an insulin-associated disease, disorder, or condition (relevant to instant claims 1 and 3); the insulin-associated disease, disorder, or condition is or comprises diabetes, obesity, cardiovascular disease, non-alcoholic fatty liver disease, Wolfram syndrome, metabolic syndrome, insulin resistance, diabetic ketoacidosis, hyperosmolar hyperglycemic state, gestational diabetes, diabetic dermadromes, diabetic neuropathy, diabetic foot ulcers, maturity onset diabetes of the young, pancreatogenic diabetes, or Polycystic ovary syndrome (PCOS) (relevant to instant claim 4); wherein the one or more microbial metabolites is or comprises a bile acid (relevant to instant claim 12); wherein the one or more microbial metabolites is or comprises tauroursodeoxycholic acid (relevant to instant claim 13); wherein one or more microbial components or microbial metabolites is butyrylcamitine, theobromine, p-hydroxyphenylpyruvic acid, propionic acid, picolinic acid, 2-hydroxy-4methylvaleric acid, N6-acetylysine, urocanic acid, N5-ethylglutamine, trigonelline, stachydrine, ectoine, 5-hydroxylysine, Arg, cholic acid, 2-(4-hydroxyphenyl)propionic acid, N- acetyltryptophan, hydroxyproline, argininosuccinic acid, Glu, sarcosine, 5- methoxyindoleacetic acid, indole-3-lactic acid, isovalerylalanine, N-acetylleucine, 1- methylhistidine, N-acetylephenylalanine, Pro, or any combination thereof (relevant to instant claim 14); wherein one or more microbial components or microbial metabolites is 4-hydroxyphenylpyruvic, ectoine, gramine, N-acetyl-L-phenylalanine, nepsilon-acetyl-L-lysine, stachydrine, trigonelline, 3-ureidopropionic acid, theobromine, hippuric acid, imidazolepropionic acid, NG-methyl-L-arginine, trans-urocanic Acid, N-acetyl-L-leucine, sarcosine, isobutyrylcarnitine, b-hydroxyisovaleric acid, L-theanine/N5-ethylglutamine, 5-hydroxylysine, phenaceturic acid, betaine, hydroxyproline, picolinic acid, 2-aminoadipic acid, glycerophosphocholine, carnitine, glycerol 3-phosphate, argininosuccinic acid, creatine, terephthalic acid, homocitrulline, mucic acid, homocysteinesulfinic acid, trimethyllysine, spermidine, glyoxylic acid, XA0013 C6H6O4S, 3-indoxylsulfuric acid, nicotinamide, N-formylglycine, ureidoglycolate, N-methylproline, glucaric acid, butyrylcarnitine, methionine sulfoxide, carboxymethyllysine, glycolic acid, phenaceturic acid, diethanolamine, phosphorylcholine, guanidinosuccinic acid, N-acetylhistidine, glyceric acid, S-methylmethionine, cysteine glutathione disulfide, kynurenine, N-acetylphenylalanine, threonic acid, malic acid, 7,8-dihydrobiopterin, homovanillic acid, taurocholic acid, 5-methoxyindoleacetic acid, butyrate, b-hydroxyisovaleric acid, 2-oxoglutaric acid, N-acetyltryptophan, thiaproline, hypotaurine, cholic acid, acetoacetic acid, ethanolamine, guanidoacetic acid, S-sulfocysteine, myristic acid C14:0 XA0027 (relevant to instant claim 15).
However, Barrangou teaches a cell that improves at least one physiological parameter associated with a disease when administered to a subject in need thereof. See claim 13 of Barrangou. The disease is selected from a group that includes cardiovascular disease, obesity, diabetes and nonalcoholic fatty liver disease (relevant to instant claims 1, 3 and 4). Nandakumar teaches administering to a subject ursodeoxycholic acid, i.e. a bile acid. See claim 24 of Nandakumar (relevant to instant claim 12). Barrangou teaches bile salt substrate including tauroursodeoxycholic acid (TUDCA). See claim 3 of Barrangou (relevant to instant claim 13). Nandakumar teaches a cholic acid supplemented diet. See p. 40 lines 39-40 (relevant to instant claims 14-15).
It would have been obvious to a person of ordinary skill in the art prior to the effective filing date of the instantly claimed invention to substitute Barrangou’s subject in need of cardiovascular disease, obesity, diabetes and/or nonalcoholic fatty liver disease treatment for the subject recited in patent claim 1, and to further combine the composition recited in patent claim 1 with Nandakumar’s bile acid, Nandakumar’s cholic acid and Barrangou’s tauroursodeoxycholic acid in order to treat an insulin-associated disease.
Conclusion
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/K.C.B./Examiner, Art Unit 1657
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