DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 1, 2023 has been considered by the examiner.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in paragraphs [0030 and 0167] in the instant published application, USPgPub 2025/0295749. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the term “NCBI”, which is a trade name or a mark used in commerce, has been noted in paragraph [0054] the instant published application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Applicant is required to properly annotate all trade names and/or marks present in the instant specification, if any additional trade names and/or marks are discovered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 44 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 44, depending from claim 33 requires that the dead bacteria spore is applied mucosally. Claim 33 requires the bacterial spore to be administered nasally, a more specific mucosal surface. Therefore, claim 44 fails to further limit claim 33. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 43, 47, and 50 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.
Regarding claims 43, 47, and 50, the term "preferably" renders each of the claims indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). In claim 43, is any coronavirus encompassed or is SARS-CoV-2 required? This same confusion arises in claims 47 and 50 following recitation of “preferably”. Are rhamnolipids or sophorolipid glycolipids required or not? In the interest of compact prosecution, the limitations recited after “preferably” are treated as merely exemplative since these terms are not precisely recited as requisite limitations.
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.
Claims 51 and 52 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature, without significantly more. Instant claim 51 recites a food stuff or dietary supplement comprising live or dead Bacillus spp. spore. Instant claim 52 recites a pharmaceutical composition comprising live or dead Bacillus spp. spore, and a pharmaceutical carrier. These materials claimed are indistinguishable from a naturally-occurring food stuff or dietary supplement, i.e., pharmaceutical, comprising live or dead Bacillus spp. spores, as evidenced by Malakar et al. (Journal of Food Protection. 2004; 67 (5): 939-946). Malakar et al. determine the presence of Bacillus spores in vegetable puree and depicts and discusses contamination in Figure 2 and “Initial contamination of spores”, bridging pages 941-942.
Similar to the fact pattern described in Myriad, natural materials are not created or altered upon isolation from its native environment. The Bacillus spores are present in harvesting, and transport of naturally grown vegetables according to Malakar et al. Therefore, the instant claims recite a natural phenomenon according to Step 2A in MPEP § 2106.04(II).
The comparison between the material claimed and the material of Malakar et al. indicates no differences in structure, function, or other characteristics. Therefore, the claimed food stuff or dietary supplement of claim 51 and the pharmaceutical composition of claim 52 comprising live or dead Bacillus spp. spores are nature exception products. See Association for Molecular Pathology v. Myriad Genetics Inc., 569 U.S. 576, 589-90 (2013) (naturally occurring things are “products of nature” which cannot be patented). Accordingly, analysis must therefore proceed to Step 2A Prong Two.
Step 2A Prong Two requires eligibility analysis to evaluate whether the claim as a whole integrates the recited judicial exception into a practical application of the exception. This evaluation is performed by (a) identifying whether there are any additional elements recited in the claim beyond the judicial exception, and (b) evaluating those additional elements individually and in combination to determine whether the claim as a whole integrates the exception into a practical application. One or more food grade ingredients, additionally recited in claim 51 and the pharmaceutical carrier of claim 52, fail to meaningfully limit the claims because it is at best the equivalent of merely adding the words “apply it” to the judicial exception. The presence of one or more food grade ingredients, or water as a pharmaceutical carrier (taught in paragraph [0157] of the instant published disclosure), does not change the nature or properties of the naturally-occurring vegetables comprising Bacillus spores. The instant claims recite no additional element that distinguishes the claimed food stuff or dietary supplement/ pharmaceutical comprising live or dead Bacillus spp. spores and the vegetables of Malakar et al. comprising live or dead Bacillus spp. spores. Accordingly, there is no recitation of an additional component that integrates the recited judicial exception into a practical application that is patent eligible pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc. -U.S.—(June 13, 2013).
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 51 and 52 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Malakar et al. (Journal of Food Protection. 2004; 67 (5): 939-946).
Malakar et al. determine the presence of Bacillus spores in vegetable puree and depicts and discusses contamination in Figure 2 and “Initial contamination of spores”, bridging pages 941-942, anticipating instant claim 51.
The ingredients of vegetable puree of Malakar et al., comprising Bacillus spores is also indistinguishable from the pharmaceutical composition of claim 52 since remaining water during blanching and pasteurization discussed in, “Survival of spores during pasteurization” on page 944 a pharmaceutically acceptable carrier, as required, and defined in paragraph [0157] of the instant published disclosure.
Claims 51 and 52 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Cutting (WO 2007/066108).
Cutting anticipate a food stuff or dietary supplement, i.e., pharmaceutical, comprising live or dead Bacillus spp. spore and one or more food grade ingredients in, “Foods, food supplements and other compositions”, beginning on page 32 and claim 18, anticipating instant claims 51 and 52.
Claims 33, 35, 36, 38, 42-44, 51, and 52 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Cutting (WO 2006/087576, cited in the IDS).
Cutting anticipates a method of treating or preventing a respiratory viral infection, see, in the third full paragraph on page 34, “In a particularly preferred instance compositions of the invention may be administered orally or nasally and in particular orally. In particular, the Bacillus will be in spore form for such administration.” In the second and third paragraphs on page 35, Cutting anticipate, “For a nasally delivered vaccine, the spore may be taken up by the nasal associated lymphoid tissue (NALT)” and “A vaccine according to the invention may give protective immunity to infection caused by any of the pathogens mentioned herein and in a preferred instance to an immunodeficiency virus, such as HIV, or another viral agent”, respectively. In the second paragraph on page 14, Cutting anticipates, “The Bacillus may also be used to provide a suitable immune response against…Coronavirus”. Coronavirus (SARS) is recited on page 15. Also see claims 1 and 19. Claims 5-8, from which claim 19 depends, lists influenza virus types A-C. These teachings anticipate instant claims 33, 36, 42, and 43 (it is not apparent from the claim that SARS-CoV-2 is required).
Regarding instant claim 35, Cutting additionally teach parenteral administration of the vaccine in the third full paragraph on page 34 and the first paragraph on page 35. It is presumed that the adaptation required to exert an adjuvant effect by the spore is achieved upon nasal placement, recited in instant claim 33. The respiratory viral vaccine of Cutting is administered by parenteral and nasal routes. Therefore, Cutting anticipate the adjuvanting effect by the spore achieved upon nasal placement.
In the first full paragraph on page 42, Cutting anticipates, “The use of the Bacillus, particularly in spore from as the delivery agent in a vaccine has the further advantage that an immune response can be elicited at the mucosal membrane. This makes the vaccination more
effective against mucosal pathogens”, as required by instant claim 38 and 44.
Claim 13 of Cutting anticipates a pharmaceutical composition comprising Bacillus bacterial spores and a pharmaceutically acceptable carrier, anticipating the dietary supplement of instant claim 51 and the pharmaceutical of instant claim 52.
Claims 34, 37, and 39-41 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Cutting (WO 2006/087576), as evidenced by Song et al. (Vaccine. 2012; 30: 3266-3277, cited in the IDS).
As discussed above, Cutting anticipates a method of treating or preventing a coronavirus and influenza virus types A-C viral infections by nasally administering Bacillus spp. spores on pages 14, 15, 34, 35, and claims 1, 5-8, and 19.
Cutting does not mention that nasal administration of the Bacillus spp. spores is an immune stimulant or an innate immune stimulant, recited in instant claim 34; that boosts sIgA in the lungs and saliva, recited in claims 37 and 39; and increases recruitment of CD4+ and CD8+ T cells.
In section 2.7, Song et al. intranasally administer Bacillus spp. spores and observe protective efficacy in Figure 5 when spore are administered alone. In section 3.5, describing Figure 5, Song et al. determine that the spores induce an innate immune response, as required by instant claim 34. In Figures 2B and 4, discussed in section 3.2, Song et al. show increased systemic and mucosal SIgA production and titer in saliva, as required in claims 37 and 39.
While Song et al. do not mention increased SIgA production in the lungs or that the bacterial spores reduce natural killer cell recruitment into the lungs following virus infection, as recited in claims 37 and 41, respectively, “a prior art reference may anticipate when the claim limitation or limitations not expressly found in that reference are nonetheless inherent in it.” See In re Oelrich, 666 F.2d at 581. Additionally, the courts have determined that “[I]nherency is not necessarily coterminus with the knowledge of those of ordinary skill in the art.” See Mehl/Biophile Int’l Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999). That is, it need not have been appreciated or recognized that the prior art reference inherently discloses the same invention for the reference to be anticipatory. See Mehl/Biophile Int’l Corp. v. Milgraum 192 F.3d 1362, 1365 (Fed. Cir. 1999); Atlas Power Co. v. Ireco Inc., 190 F.3d 1342, 1347 (Fed. Cir. 1999). Since Song et al. teach increased systemic and mucosal SIgA production and recognize that “secretory IgA (sIgA) from the respiratory tract is more effective in cross-protection against heterologous influenza compared to IgG induced by parenteral vaccination”, increased SIgA titers are inherently expressed in the lungs.
Regarding bacterial spores reducing natural killer cell recruitment into the lungs following virus infection, sections 2.8 and 3.4 of Song et al. describe a priming with inactivated influenza virus with spores, boosting 14 days later with the same composition, and challenging 4 weeks after the boosting dose. Example 7 and Figure 13D of the instant published disclosure (USPgPub 2025/0295748) depicts a reduction of natural killer cell recruitment into the lungs following virus infection following spore pre-treatment. Since Song et al. pre-treats subjects with spores prior to influenza virus challenge, the phenomenon of a reduction in natural killer cell recruitment into the lungs following virus infection, is an inherent occurrence, consistent with the findings in Mehl/Biophile Int’l Corp. v. Milgraum, 192 F.3d 1362, 1365 (Fed. Cir. 1999).
In section 3.2, and Figure 3 of Song show elevated IL-2 and IFN-γ cytokine expression produced by (CD4+) Th1 cells and IL-6 produced by (CD4+) Th2 cells, as required by instant claim 40.
Therefore, Song et al. describe the innate immune stimulation accompanied by increased secretion of sIgA in the lungs and saliva, increased recruitment of CD4+ and CD8+ T cells upon nasal administration of Bacillus spp. spores, increased SIgA production in the lungs, and the reduction of natural killer cell recruitment into the lungs following virus infection following pre-treatment with bacterial spores, inherently anticipated in the method of treating or preventing a coronavirus and influenza virus types A-C viral infections by nasally administering Bacillus spp. spores on pages 14, 15, 34, 35, and claims 1, 5-8, and 19 of Cutting.
Claims 45, 46, and 49 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Cutting (WO 2006/087576), as evidenced by the admitted prior art of Takigawa et al. (Journal of natural products. 2010 Feb 26; 73 (2): 204-207) in paragraphs [0057-0060] of the instant disclosure (USPgPub 2025/0295748).
As discussed above, Cutting anticipates a method of treating or preventing a coronavirus and influenza virus types A-C viral infections by nasally administering Bacillus spp. spores on pages 14, 15, 34, 35, and claims 1, 5-8, and 19.
Cutting does not mention the Bacillus spp. spores comprise a squalene cyclase gene (sqhC), recited in instant claim 45 or that the bacterial spore produces or comprises a sporulene family member, required in instant claims 46 and 49.
Paragraphs [0057-0060] of the instant published disclosure points to the teachings of Takigawa et al. Paragraph [0060] is reproduced below:
[0060] Sporulenes A, B and C are believed to be derived from C35-terpenes, via the enzyme squalene cyclase, as shown in FIG. 1 of Takigawa H, Sugiyama M, Shibuya Y. C(35)-terpenes from Bacillus subtilis KSM 6-10. J Nat Prod. 2010; 73(2):204-7; doi: 10.1021/np900705q.
In the first paragraph under the abstract, Takigawa et al. teach B. subtilis produces three pentacyclic terpenoids (sporulenes (required in claim 46)) via the enzyme squalene cyclase, recited in claim 45.
Since Cutting anticipate a method of treating or preventing a coronavirus and influenza virus types A-C viral infections by nasally administering Bacillus subtilis spores on pages 14, 15, 34, 35, and claims 1, 2, 3, 5-8, and 19, the Bacillus subtilis spores of Cutting comprises a sporulene family member, as required in the method of instant claim 49.
MPEP § 2129 : A statement by an applicant in the specification or made during prosecution identifying the work of another as "prior art" is an admission which can be relied upon for both anticipation and obviousness determinations, regardless of whether the admitted prior art would otherwise qualify as prior art under the statutory categories of 35 U.S.C. 102. Riverwood Int’l Corp. v. R.A. Jones & Co., 324 F.3d 1346, 1354, 66 USPQ2d 1331, 1337 (Fed. Cir. 2003); Constant v. Advanced Micro-Devices Inc., 848 F.2d 1560, 1570, 7 USPQ2d 1057, 1063 (Fed. Cir. 1988).
Claims 47 and 50 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Cutting (WO 2006/087576), as evidenced by Vanittanakom et al. (The Journal of antibiotics. 1986; 39 (7):888-901* Note: due to a technical glitch, a copy of this reference could not be attached to this Office action, but the reference can be accessed at the following link: https://www.jstage.jst.go.jp/article/antibiotics1968/39/7/39_7_888/_pdf/-char/en), Wörmann et al. (Molecular microbiology. 2011 Feb;79(3):566-83) and Olishevska et al. (Applied Microbiology and Biotechnology (2019) 103:1189–1215).
Cutting anticipates a method of treating or preventing a coronavirus and influenza virus types A-C viral infections by nasally administering Bacillus spp. spores on pages 14, 15, 34, 35, and claims 1, 5-8, and 19.
Cutting does not mention the Bacillus spp. spores comprising a non-ribosomal lipopeptide from the fengycin family.
Vanittanakom et al. teach fengycin is an antifungal lipopeptide produced by Bacillus subtilis, see the title.
Since Cutting anticipate a method of treating or preventing a coronavirus and influenza virus types A-C viral infections by nasally administering Bacillus subtilis spores on pages 14, 15, 34, 35, and claims 1, 2, 3, 5-8, and 19, the Bacillus subtilis spores of Cutting produce fengycin, as required in the method of instant claim 47(i).
Cutting does not mention the Bacillus spp. spores further produce or comprise a glycolipid.
Wörmann et al. teach Bacillus subtilis produces a glycolipid, GroP-Glc2-DAG, see the abstract and Introduction.
Since Cutting anticipate a method of treating or preventing a coronavirus and influenza virus types A-C viral infections by nasally administering Bacillus subtilis spores on pages 14, 15, 34, 35, and claims 1, 2, 3, 5-8, and 19, the Bacillus subtilis spores of Cutting produce a glycolipid, as required in the method of instant claims 47(ii) and 50(i).
Cutting does not mention the Bacillus spp. spores further produce or comprise a Mycosubtilin lipopeptide.
Olishevska et al. teach Bacillus subtilis produces Mycosubtilin, see the last entry of Table 3 on page 1197.
Since Cutting anticipate a method of treating or preventing a coronavirus and influenza virus types A-C viral infections (recited in claim 50(iii)) by nasally administering Bacillus subtilis spores on pages 14, 15, 34, 35, and claims 1, 2, 3, 5-8, and 19, the Bacillus subtilis spores of Cutting produce Mycosubtilin, as required in the method of instant claims 47(iii) and 50(ii).
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.
Claim 48 is rejected under 35 U.S.C. 103 as being unpatentable over Cutting, as applied to claims 33, 35, 36, 38, 42-44, 51, and 52 above, and further in view of instant SEQ ID NO: 1 alignment with GenEmbl db access no CP034037 Dec 2018 and Huang et al. (Scientific reports. 2016 Feb 19;6(1):21363).
See the teachings of Cutting above.
Cutting does not teach SEQ ID NO: 1, as required.
GenEmbl db access no CP034037 Dec 2018 shares 99.9% (rounds to 100%) sequence identity to SEQ ID NO: 1, see the alignment provided. The source of the sequence is derived from B. amyloliquefaciens.
Paragraph [0041] of the instant published disclosure (USPgPub 2025/0295748) states:
Recent changes in the bacterial taxonomy include the reclassification of B. amyloliquefaciens strains as B. velezensis (Wang et al, 2008; Fan, B., Blom, J., Klenk, H. P. & Borriss, R. Bacillus amyloliquefaciens, Bacillus velezensis, and Bacillus siamensis Form an “Operational Group B. amyloliquefaciens” within the B. subtilis Species Complex. Front Microbiol 8, 22, doi:10.3389/fmicb.2017.00022 (2017)).
Cutting does not mention B. amyloliquefaciens strains or B. velezensis.
Huang et al. teach B. amyloliquefaciens, see the title.
One of ordinary skill in the art prior to the instant effective filing date would have been motivated to have nasally administered the B. amyloliquefaciens of Huang et al., expressing the GenEmbl db access no CP034037 nucleic acid in the method of Cutting because Huang et al. teach nasal administration of Bacillus amyloliquefaciens induces dendritic cell maturation and enhances the immune response against inactivated avian influenza virus compared to immunization with inactivated H9N2 AIV alone. See the abstract; Figures 1, 3, and 4; SQR9 facilitates the H9N2 WIV-induced recruitment of submucosal DCs and antigen capture in cervical lymph nodes (CLNs); Specific sIgA levels in the respiratory tract; and Specific IgG levels in serum. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have nasally administered the B. amyloliquefaciens of Huang et al., expressing the GenEmbl db access no CP034037 nucleic acid in the method of Cutting because both Huang et al. and Cutting nasally administer Bacillus spp. as a mucosal adjuvants with influenza virus vaccines, see the Introduction and Figures 1, 3, and 4 of Huang et al. and pages 14, 15, 34, 35, and claims 1, 2, 3, 5-8, and 19 of Cutting.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
De Souza et al. (PLoS One. 2014 Jan 27; 9 (1): e87454) review Bacillus subtilis spores as adjuvants in vaccine formulations.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHANON A FOLEY whose telephone number is (571)272-0898. The examiner can normally be reached M-F, generally 5:30 AM-5 PM, flexible.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael D. Allen can be reached at 571-270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Shanon A. Foley/Primary Examiner, Art Unit 1671