DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The amendment filed September 2, 2026, has been received and entered.
Claims 2-6, 10, 12, 14, 16-19, 23, 34, 36, and 40 are cancelled.
Claims 1, 7-9, 11, 13, 15, 20-22, 24-33, 35, 37-39, and 41 are pending.
Election/Restrictions
Applicant’s election of Group I and the species (a) enzyme to degrade an amine, specifically diamine oxidase enzyme (DAO), (b) amine oxidizing bacteria, (c) irritable bowel syndrome (IBS), and (d) Raoultella ornithinolytica (claims 1, 13, 20-21, 27-30, 32, 33, 35, and 37), in the reply filed on September 2, 2026, is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 7-9, 11, 15, 22, 24-26, 31, 38, 39, and 41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 13, 20, 21, 27-30, 32, 33, 35, and 37 are examined on the merits.
Information Disclosure Statement
The information disclosure statement filed September 9, 2024, fails to comply with 37 CFR 1.98(a)(2), which requires a legible copy of each cited foreign patent document; each non-patent literature publication or that portion which caused it to be listed; and all other information or that portion which caused it to be listed. It has been placed in the application file, but the information referred to therein has not been considered. In particular, no copy has been filed of WO 2014/152754 A2.
Drawings
The drawings are objected to because Figures 8A-8E are not legible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 13, 20, 28-30, 32, 33, 35, and 37 are objected to because of the following informalities:
Claim 13 is objected to because the recitation “gamma-glutamyl-gamma-aminobutraldehyde dehydrogenase” in lines 22-23 is a misspelling of the term “gamma-glutamyl-gamma-aminobutyraldehyde dehydrogenase.”
Also, claim 13 is objected to because the recitation “4-aminobutyradldehyde dehydrogenase” in the last line is a misspelling of the term “4-aminobutyraldehyde dehydrogenase.”
Claim 20 is objected to because the recitation “the enzyme to degrade an amine….and further comprise an enzyme that degrade…” is not grammatically correct. The recitation “comprise” should be substituted with the word “comprises,” and the recitation “degrade” should be substituted with the word “degrades.”
Claim 28 is objected to because the space between the recitation “tryptasemia” and the comma in the last line should be deleted.
Claim 29 is objected to because the recitation “or” after the recitation “Escherichia coli,” should be deleted.
Also, claim 29 is objected to because the recitation “penumoniae” in line 7 is a misspelling of the term “pneumoniae.”
Furthermore, claims 29 and 30 are objected to because the recitation “or” in the last line of both claims should not be italicized.
Claim 32 is objected to because the recitation “or” after the recitation “Escherichia coli,” should be deleted.
Also, claim 32 is objected to because the recitation “penumoniae” in line 7 is a misspelling of the term “pneumoniae.”
Furthermore, claim 32 is objected to because the recitation “or” after the recitation “Proteobacteria spp.,” in line 8 should be deleted.
Since claim 32 is objected to, then its dependent claims, claims 33, 35, and 37, are objected to.
Claim 33 is objected to because the recitation “or” after the recitation “Escherichia coli,” in line 5 should be deleted.
Also, claim 33 is objected to because the recitation “detecting a quantity of one or more of the following microorganisms:” in line 7 should be deleted because it repeats the preceding phrase.
Claim 33 is objected to because the recitation “penumoniae” in line 8 is a misspelling of the term “pneumoniae.”
Furthermore, claim 33 is objected to because the recitation “or” after the recitation “Proteobacteria spp.,” in the last line should be deleted.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 13, 20, 28, 32, 33, 35, and 37 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 13 is indefinite because it is unclear how “the enzyme” of line 2 can be selected from the chemicals recited in lines 3-7. None of the chemicals recited in lines 3-7 are enzymes.
Also, claim 13 is indefinite because it is unclear how “the enzyme to degrade an amine” in line 9, which is directed to a single enzyme, comprises two enzymes (“or both” in line 10).
Claim 13 is indefinite because it is unclear how “the enzyme to degrade an amine” in line 13, which is directed to a single enzyme, comprises a combination of enzymes (“combinations thereof” in line 16). A single enzyme cannot comprise a plurality of enzymes.
Also, claim 13 is rendered indefinite by the recitations “gamma-glutamylcadaverine oxidoreductase” and “aminopropylcadverine synthase” (or the spelling “aminopropylcadaverine synthase”) in lines 15 and 18, respectively. These terms are not terms of the art, as determined by a search. Therefore, these enzymes are unclear.
Furthermore, claim 13 is indefinite because it is unclear how “the enzyme to degrade an amine” in line 17, which is directed to a single enzyme, comprises a combination of enzymes (“combinations thereof” in the last line). A single enzyme cannot comprise a plurality of enzymes.
Claim 20 is indefinite because it is unclear how “the enzyme to degrade an amine” in lines 1-2, which is directed to a single enzyme and comprises diamine oxidase, can further comprise “an enzyme that degrade histamine, putrescine, cadaverine, spermidine, spermine or combinations thereof.” A single enzyme cannot comprise a plurality of enzymes.
Claim 28 is indefinite because it is unclear how “the biogenic amine related condition” in lines 1-2, which is directed to a single condition, is a combination of conditions (“combinations thereof” in the last line). A single condition cannot be a plurality of conditions.
Claim 32 is rendered indefinite by the recitation “selecting a therapy for the subject” in line 9. It is unclear whether the “therapy” is a “therapy for a biogenic amine related condition.” Since claim 32 is indefinite, then its dependent claims, claims 33, 35, and 37, are rendered indefinite. Thus, claims 32, 33, 35, and 37 are rejected under 35 U.S.C. 112(b). This rejection can be overcome by amending line 9 of claim 32 to recite “selecting a therapy for a biogenic amine related condition for the subject.”
Also, claim 32 is indefinite because it is unclear how the detecting step relates to the subject since claim 32 does not recite that the detection is performed on the subject. Since it is not clear that the quantity of one or more of the microorganisms is detected in the subject, then it is confusing how said quantity relates to selecting a therapy for the subject. Since claim 32 is indefinite, then its dependent claims, claims 33, 35, and 37, are rendered indefinite. Thus, claims 32, 33, 35, and 37 are rejected under 35 U.S.C. 112(b).
Notice Re: Prior Art Available Under Both Pre-AIA and AIA
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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, 13, 20, 21, and 27 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Lyte (WO 2021/133877. Listed on IDS filed 9/2/26).
Lyte discloses the use of histamine degrading enzymes able to degrade histamine for treating a subject having conditions associated with histamine overproduction (page 4, lines 1-3). Also, the histamine degrading enzymes are used for the control of histamine in a subject (abstract). Histamine is a biogenic amine (page 15, lines 1-2). The methods include administering to the subject a therapeutically effective amount of the histamine degrading enzyme (page 32, lines 5-6). Therefore, Lyte teaches a method of treating a biogenic amine related condition (condition associated with histamine overproduction) in a subject in need thereof, reducing one or more symptoms in a subject having a biogenic amine related condition, or decreasing biogenic amine level in a subject having a biogenic amine related condition (through the control of histamine), comprising administering to the subject a therapy that is an enzyme to degrade an amine (histamine degrading enzyme, i.e., an enzyme to degrade histamine which is an amine). Therefore, Lyte anticipates instant claim 1 (elected species, an enzyme to degrade an amine).
Regarding instant claim 13, Lyte teaches that the histamine degrading enzyme can be a amine oxidase (copper containing), specifically diamine oxidase (DAO) (page 20, lines 9-10 and 19-20; page 23, lines 7-8; claim 24 of Lyte). Therefore, Lyte anticipates instant claim 13 (elected species, diamine oxidase).
Regarding instant claim 20, the histamine-degrading enzymes can be diamine oxidase and/or histamine oxidase (claim 24 of Lyte). Therefore, the enzymes to degrade an amine of Lyte comprises diamine oxidase (DAO), and further comprises an enzyme that degrades histamine (histamine oxidase), anticipating instant claim 20.
Regarding instant claim 21, Lyte discloses that the enzymes can be coated to protect their activity during transit through the gut until they reach specific section of gut where the need for histamine degradation exists (page 22, lines 11-13). The histamine degrading enzymes may be administered to reach the gut in a tablet form (page 25, lines 6-7), and the tablets may be coated such as with hydroxypropyl methylcellulose phthalate (page 25, lines 20-24). Therefore, instant claim 21 is anticipated.
Regarding instant claim 27, Lyte discloses the embodiment of using a composition containing both a histamine degrading enzyme and a probiotic (abstract; claim 22 of Lyte; page 27, lines 15-16; page 32, lines 5-6). The probiotic can be incorporated and processed to release enzymes contained within that can break down histamine in the gut, wherein exemplary enzymes include amine oxidase (copper containing) (page 20, lines 7-10). Bacteria can possess the activity of amine oxidase (copper containing) (page 20, lines 21-24). A probiotic bacteria that releases amine oxidase (copper containing) is directed to an ‘amine oxidizing bacteria.’ Therefore, instant claim 27 (elected species, amine oxidizing bacteria) is anticipated.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over Lyte in view of Neree (Scientific Reports. 2020. 10: 21563. 13 pages).
As discussed above, Lyte anticipates claims 1, 13, 20, 21, and 27. However, Lyte differs from claim 28 in that Lyte does not expressly disclose that the condition associated with histamine overproduction (directed to a ‘biogenic amine related condition) that is treated is irritable bowel syndrome (IBS) (elected species).
Neree discloses that in the gut lumen, histamine is mainly catabolized by intestinal diamine oxidase (iDAO) (page 2, fifth paragraph). Also, iDAO levels are often decreased by intestinal dysfunctions such as irritable bowel syndrome, with the result that amounts of histamine largely exceed the capacity of iDAO to decompose it (page 2, fifth paragraph). The results of Neree’s study led to the conclusion that administration of vegetal diamine oxidase (vDAO) in the gut lumen is a valid alternative treatment for histamine-induced intestinal dysfunctions (abstract).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to use the method of Lyte to treat irritable bowel syndrome. One of ordinary skill in the art would have been motivated to do this because, based on Neree, irritable bowel syndrome is a condition associated with histamine overproduction (which is treated by Lyte) given that histamine exceeds the capacity of intestinal diamine oxidase decreased in irritable bowel syndrome. Additionally, there would have been a reasonable expectation of treating irritable bowel syndrome with the method of Lyte because Neree indicates that administration of vegetal diamine oxidase (which is directed to a histamine degrading enzyme, the active agent of Lyte) in the gut lumen could be a valid alternative treatment for histamine-induced intestinal dysfunctions. Therefore, instant claim 28 (elected species, irritable bowel syndrome) is rendered obvious.
Claims 29, 30, 32, 33, and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Lyte in view of Smolinska (Allergy. 2013. 69(3): 273-281. Listed on IDS filed 9/2/26).
As discussed above, Lyte anticipates claims 1, 13, 20, 21, and 27. However, Lyte differs from claims 29 and 30 in that Lyte does not expressly disclose that the subject has been detected to have a quantity of Raoultella ornithinolytica (elected species) higher than the microorganism’s reference value. Regarding claims 32, 33, and 37, Lyte differs from the claims in that Lyte does not expressly disclose detecting a quantity of Raoultella ornithinolytica (elected species), and selecting their therapy (histamine degrading enzyme, e.g., diamine oxidase, which is directed to the elected species of the claimed ‘enzyme to degrade an amine’) for the subject when the quantity of one or more of the R. ornithinolytica is higher than its reference value.
Smolinska is a review discussing the immunoregulatory influence of histamine on a number of gastrointestinal disorders, including scombroid food poisoning (abstract). Scombroid poisoning is also known as histamine fish poisoning, and involves histamine and other decomposition products generated in fish tissues by bacterial conversion of free histidine (page 276, left column, last paragraph). The histamine is produced by a wide range of bacteria, including Raoultella ornithinolytica (page 276, left column, last paragraph). Also, in scombroid poisoning, histamine toxicity is potentiated by the action of diamine oxidase (DAO) inhibitors that are also present together with dietary histamine in the ingested fish (page 276, right column, second paragraph).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to use the method of Lyte to treat scombroid poisoning. One of ordinary skill in the art would have been motivated to do this because, based on Smolinska, scombroid poisoning is a condition associated with histamine overproduction (which is treated by Lyte) given that scombroid poisoning is histamine poisoning/toxicity. Additionally, there would have been a reasonable expectation of treating scombroid poisoning with the method of Lyte because diamine oxidase inhibitors are present in the ingested fish which potentiate histamine toxicity; this would suggest that diamine oxidase, a histamine degrading enzyme disclosed in Lyte, administered at a level to overcome the inhibition capacity of the diamine oxidase inhibitors present in the ingested fish could counteract the histamine toxicity of the condition.
Further still, in order to treat scombroid poisoning with the method of Lyte, one of ordinary skill in the art would have been motivated to detect the quantity of Raoultella ornithinolytica in the subject before the treatment, and if the quantity is greater than zero (directed to the microorganism’s ‘reference value’), then the histamine degrading enzyme (e.g., diamine oxidase) is administered. One of ordinary skill in the art would have been motivated to do this in order to ascertain that the subject indeed has scombroid poisoning that would have been expected to be treatable by the method of Lyte. The skilled artisan would have expected that the presence of Raoultella ornithinolytica is indicative of scombroid poisoning because Raoultella ornithinolytica is a histamine-producing bacteria in fish. Therefore, instant claims 29 (elected species, R. ornithinolytica), 30 (elected species, R. ornithinolytica), 32 (elected species, R. ornithinolytica and an ‘enzyme to degrade an amine’), 33 (elected species, R. ornithinolytica), and 37 are rendered obvious.
Claim 35 is rejected under 35 U.S.C. 103 as being unpatentable over Lyte and Smolinska as applied to claims 29, 30, 32, 33, and 37 above, and further in view of Zilberstein (Clinics. 2007. 62(1): 47-54).
As discussed above, Lyte in view of Smolinska renders obvious claims 29, 30, 32, 33, and 37. The references differ from claim 35 in that they do not expressly disclose that the detection is made in a biological sample obtained from the subject, wherein the biological sample comprises small bowel aspirate, gut mucosal biopsies, blood, breath, or a combination thereof.
Zilberstein discloses a study for standardizing the methods of sample collection of mucus from the digestive tract and to determine the microbiota in healthy volunteers from Brazil (Purpose in abstract). After collection from the digestive tract, the mucus samples were taken to the microbiology laboratory (page 49, left column, first paragraph). The collected samples were placed in selective culture media for aerobic and anaerobic microorganisms and yeast (page 49, right column second paragraph). The concentrations and prevalence of different microorganisms found in the mucus in each segment of the digestive tract were determined (page 50, left column, third to fifth paragraphs).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to detect the quantity of R. ornithinolytica in a gut mucosal biopsy sample obtained from the subject when performing the method rendered obvious by Lyte in view of Smolinska. One of ordinary skill in the art would have been motivated to do this because gut mucus samples from the digestive tract are recognized samples for the detection of microbiota in the digestive tract of a subject. Since the R. ornithinolytica is present in the fish consumed by the subject that causes the scombroid poisoning for the method rendered obvious by Lyte in view of Smolinska, then the R. ornithinolytica would have been expected to be in the gut mucosal biopsy sample of the subject if the subject has scombroid poisoning. Therefore, instant claim 35 (gut mucosal biopsies) is rendered obvious.
Conclusion
No claims are allowed.
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Sef
/SUSAN E. FERNANDEZ/Examiner, Art Unit 1651
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