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, 3-12, and 14-20 are pending. Claims 17-20 remain withdrawn. Claims 1, 3-12, and 14-16 are under examination.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
(Maintained) Claims 1, 3-11, and 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over Woodward et al. (US 20220226396 A1, published 21 July 2022, effectively filed 12 May 2019) in view of Kiba et al. (Flow-injection determination of L-histidine with an immobilized histidine oxidase from Brevibacillus borstelensis KAIT-B-022 and chemiluminescence detection, Analytical Sci, 2006 Jan;22(1):95-8).
Regarding claims 1 and 15-16, Woodward teaches a probiotic composition comprising Brevibacillus borstelensis, (Woodward [0034] and Table 5 pgs. 46-47), which is orally administered to a subject (Woodward [0169]), and comprises 103-1010 CFU (Woodward [0405]).
Woodward does not teach that the administered probiotic composition comprises a histamine degrading enzyme, nor that the administered probiotic composition controls histamine production.
Regarding claims 1, 7-11, and 15-16, Kiba teaches a Brevibacillus borstelensis strain comprising a histidine degrading enzyme called histidine oxidase which controls levels of histamine (Kiba Intro para. 3). Kiba teaches that the histidine oxidase is produced by the cells of Brevibacillus borstelensis, and also purified histidine oxidase from cell-free extracts of Brevibacillus borstelensis (Kiba Materials and methods para. 1 pg. 95-96, relevant for claim 8). Kiba also teaches that high tissue levels of histamine cause swelling, inflammation, and allergic reactions in a subject (Kiba Intro para. 1).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to add Kiba’s Brevibacillus borstelensis (comprising histidine degrading enzyme, histidine oxidase) to Woodward’s probiotic composition comprising Brevibacillus borstelensis, Bacillus megaterium, and Bacillus subtilis, and administer the modified probiotic composition to a subject in order to control histamine production, and/or treat inflammatory diseases and allergic reactions caused by high tissue histamine levels in the subject, as suggested by Kiba. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because Kiba taught that Brevibacillus borstelensis comprises the enzyme histidine oxidase capable of degrading histidine and controlling histamine production, and that high tissue levels of histamine cause swelling, inflammation, and allergic reactions in a subject (Kiba Intro para. 1).
Regarding claim 3 and 14, Woodward teaches the probiotic composition comprising Brevibacillus borstelensis also comprises Bacillus megaterium and/or Bacillus subtilis (Woodward Table 5 pgs. 46-47)
Regarding claims 4-6, Woodward teaches that the composition is administered to humans, dairy cattle, poultry, chicken, turkey, goose, duck, fish, shellfish, sheep, pig, or companion animals (Woodward [0084], [0102], [0105], and [0429].
(Maintained) Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Woodward in view of Kiba as applied to claims 1, 3-11, and 14-16 above, and further in view of Branco et al. (Role of Histamine in Modulating the Immune Response and Inflammation, Hindawi, Mediators of Inflammation Volume 2018, Article ID 9524075, 10 pages, 27 August 2018).
Woodward and Kiba do not teach treating inflammatory and/or immunological diseases clostridial dermatitis, clostridial enteric disease, gut inflammation, necrotizing enterocolitis, neoplastic disease, and/or bacterial infection.
Branco teaches that several inflammatory and/or immunological conditions are linked to elevated histamine levels within a subject, including autoimmune diseases, inflammatory skin diseases (dermatitis), cancers (neoplastic diseases), and gut and pulmonary inflammation (Branco Intro para. 1). Branco also teaches that elevated histamine levels induce proinflammatory mediators and cytokines in several different cells (Branco Abstract).
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to use the method of controlling histamine levels and treating inflammatory and/or immunological diseases as taught by Woodward in view of Kiba to treat inflammatory and/or immunological autoimmune diseases, inflammatory skin diseases (dermatitis), cancers (neoplastic diseases), and gut and pulmonary inflammation, as suggested by Branco. One of ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, because Branco taught that autoimmune diseases, inflammatory skin diseases (dermatitis), cancers (neoplastic diseases), and gut and pulmonary inflammation are linked to elevated levels of histamine in a subject, so one of ordinary skill in the art would understand that reducing or controlling the concentration of histamine in a subject afflicted with these inflammatory and/or immunological diseases would predictably treat those histamine-mediated diseases.
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.
(Maintained) Claims 1, 3-12, and 14-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over conflicting claims 1, 6-8, 10, 12, 14, and 17-20 of copending Application No. 17/757,963 (reference application) in view of Kiba et al. (Flow-injection determination of L-histidine with an immobilized histidine oxidase from Brevibacillus borstelensis KAIT-B-022 and chemiluminescence detection, Analytical Sci, 2006 Jan;22(1):95-8) and Lee et al. (Degradation of histamine by Bacillus polymyxa isolated from salted fish products, Journal of food and drug analysis 23 (2015) 836-844).
Regarding instant claims 1, 7-8, and 11-12, conflicting claims 1 and 12, and 14 recite a probiotic composition and a method of preventing and/or treating clostridial dermatitis, clostridial enteric disease, a clostridial infection and/or gut inflammation in a subject by administering a probiotic composition to the subject, wherein the probiotic composition comprises a histamine-degrading bacteria comprising Brevibacterium aureum, Brevibacterium sediminis, and/or, Brevibacterium epidermis, and wherein the probiotic composition controls histamine production from a commensal microbiota. Thus, the active administration step of the conflicting claims leads to the control of histamine levels in a subject, and is also capable of treating inflammatory diseases mediated by histidine.
However, the conflicting claims do not recite that the probiotic composition may comprise Brevibacillus borstelensis, Brevibacillus brevis, and/or Brevibacillus parabrevis.
Kiba teaches a Brevibacillus borstelensis strain comprising a histidine degrading enzyme, histidine oxidase (Kiba Intro para. 3). Kiba teaches that the histidine oxidase is produced by the cells of Brevibacillus borstelensis, and also purified histidine oxidase from cell-free extracts of Brevibacillus borstelensis (Kiba Materials and methods para. 1 pg. 95-96, relevant for claim 8). Kiba also teaches that high tissue levels of histamine cause swelling, inflammation, and allergic reactions in a subject (Kiba Intro para. 1).
It would have been prima facie obvious to one of ordinary skill in the art to use Kiba’s Brevibacillus borstelensis in the probiotic composition administered in the method recited in the conflicting claims. One of ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, because Kiba teaches Brevibacillus borstelensis comprises a histidine degrading enzyme, histidine oxidase, that is suitable for controlling histamine production in the subject of the conflicting claims and thus treating histidine mediated inflammatory disease in a subject.
Regarding instant claims 3 and 14, conflicting claim 12 also recites that the probiotic composition also comprises one or more of Bacillus spp.
However, the conflicting claims do not recite that the probiotic composition comprises the Bacillus species Bacillus flexus, Bacillus megaterium, and/or Bacillus subtilis.
Lee teaches that several species of Bacillus, including Bacillus subtilis, can degrade histamine (Lee Table 1), and Bacillus megaterium possesses histamine degrading enzymes (Lee Pg. 840 para. 5 sentence 2), and as such is capable of degrading histamine.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the present invention to combine Kiba’s Brevibacillus borstelensis and Lee’s Bacillus subtilis and Bacillus megaterium in the probiotic composition administered in the method recited in the conflicting claims. One of ordinary skill in the art would have been motivated to do so, and have a reasonable expectation of success, because Kiba teaches Brevibacillus borstelensis comprises a histidine degrading amine enzyme, histidine oxidase, that is suitable for controlling histamine production in the subject of the conflicting claims, and Lee teaches that Bacillus subtilis and Bacillus megaterium can degrade histamine and possess histamine degrading enzymes.
Regarding instant claims 4-6, conflicting claims 6-8 and 10 recite that the composition may be administered to chicken, duck, goose, turkey, guinea fowl, ostrich, pigeon, quail, pheasant, companion animals, aquaculture species, and humans.
Regarding instant claim 9, conflicting claim 17 recites the probiotic composition is a live, non-pathogenic microorganism, a spore that is germinated into a histamine-degrader in the subject, or a mash incorporating a microorganisms therein.
Regarding instant claim 10, conflicting claim 18 recites the composition is neat, coated, or encapsulated and administered in a feed source.
Regarding instant claim 15, conflicting claim 19 recites that the probiotic is therapeutically effective at a concentration between 104 to 1014 CFU.
Regarding instant claim 16, conflicting claim 20 recites the composition is administered orally or topically.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 27 February 2026 have been fully considered but they are not persuasive.
Regarding Applicant’s arguments that Woodward is non-analogous art and that Woodward and Kiba do not teach or suggest control of histamine production (Remarks pg. 6-7 briding para.), Woodward teaches administering a probiotic composition comprising Brevibacullus borstelensis, Bacillus megaterium, and Bacillus subtilis. Kiba teaches a Brevibacullus borstelensis bacteria comprising a histidine oxidase, which is able to control histamine production in a subject by degrading histamine’s required precursor compound: histidine. As evidenced by Kucher et al. (Genes of the Histamine Pathway and Common Diseases, Russian Journal of Genetics, 2018, Vol. 54, No. 1, pp. 12–26. © Pleiades Publishing, Inc., 2018), histamine is biochemically synthesized from histidine by the enzyme histidine decarboxylase (Kucher Fig. 1 and pg. 13 left col para. 2). Because of this biochemical relationship, Kiba’s Brevibacullus borstelensis histidine oxidase’s degradation of histidine consequently controls the levels of histamine. Since Woodward teaches the administration of a probiotic composition comprising Brevibacullus borstelensis to a subject and Kiba teaches an advantageous effect of Brevibacullus borstelensis being able to control histamine production, one of ordinary skill in the art would have found it obvious to administer a probiotic composition comprising Brevibacullus borstelensis to a subject in order to control histamine production in the subject. The reasonable expectation of success comes from Woodward, who discloses the successful administration of a probiotic composition into a subject, so one of ordinary skill in the art would reasonably expect success in administering Kiba’s Brevibacullus borstelensis.
Regarding Applicant’s arguments that Examiner mistakenly characterized Kiba as teaching a Brevibacullus borstelensis strain comprising a histamine degrading enzyme, which is inconsistent with Kiba’s disclosure, and that Kiba’s Brevibacullus borstelensis does not control histamine levels in a subject (Remarks pg. 7-8 bridging para.), the rejection had a typographical error that affected the interpretation of the rejection. Kiba teaches a Brevibacullus borstelensis strain comprising histidine oxidase, not a histamine oxidase. This typographical error has been corrected in the rejections above. As discussed above, Kiba teaches a Brevibacullus borstelensis bacteria comprising a histidine oxidase that controls histamine production by degrading histamine’s required precursor compound: histidine, as evidenced by fig. 1 and pg. 13 left col para. 2 of Kucher. Because of this biochemical relationship, Kiba’s Brevibacullus borstelensis histidine oxidase’s degradation of histidine consequently lowers/controls the levels of histamine.
Regarding Applicant’s arguments that Kiba frames dietary histidine and histamine formation in foods, but does not teach in vivo histamine control in living subjects (Remarks pg. 8 paras. 2-3), Kiba demonstrates that Brevibacullus borstelensis’s histidine oxidase was effective at degrading histidine, which in turn lowers and controls histamine levels, as discussed above. Although Kiba does not explicitly provide data showing in vivo control of histamine levels, the in vitro results of Kiba reasonably suggest to one of ordinary skill in the art that the histidine degradation results could be achieved in vivo as well, because in vivo and in vitro results often correlate. No evidence has been provided that would lead one of ordinary skill in the art to conclude otherwise, either by Kiba themselves or by Applicant. Thus, based on the teachings and knowledge in the art, one of ordinary skill in the art would reasonably conclude that Kiba’s Brevibacullus borstelensis and its histidine oxidase would control histamine production in a subject in need thereof.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Alexander M Duryee whose telephone number is (571)272-9377. The examiner can normally be reached Monday - Friday 9:00 am - 5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Louise Humphrey can be reached on (571)-272-5543. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Alexander M Duryee/Examiner, Art Unit 1657
/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
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