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 .
Status of claims
Claims 25, 27, 29, 30, 32-37 and 39-46 as amended 10/01/2025 are pending.
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 25, 27, 29, 30, 32-37 and 39-45 as amended are/remain rejected under 35 U.S.C. 103 as being unpatentable over US 9,463,209 (Bauer et al), Rial et al ( Microbes and Infection, 2016, 18, pages 747-757), Kearny et al (Ann Allergy Asthma Immunol. 2015, pages 1-6) and Ellis et al (“Comparative efficacy of intranasal and oral vaccines against Bordetella bronchiseptica in dogs”. The Veterinary Journal, 2016, 212, pages 71-77).
US 9,463,209 (Bauer et al) teaches a method of treating or preventing respiratory disorders or respiratory infections (abstract; col. 9, lines 6-11; col. 38, line 44; col. 41, line 3) in a subject in need thereof, wherein the method comprises administering to said subject a therapeutically effective amount of bacterial extract obtainable by alkaline lysis (col. 5, lines 29 and 63; col. 37, lines 38-39) of Gram positive or Gram-negative bacterial species (col. 7, lines 56-67). The bacteria are
chosen from Moraxella catarrhalis, Haemophilus influenzae, Klebsiella pneumoniae, Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes and Streptococcus sanguinis (col. 1, lines 29-35). The alkaline lysis is conducted at pH greater than 10 (col. 37, lines 38-39). The subjects under treatment are mammalians including humans and animals (col. 4, lines 58-60; col. 38, lines 40-41). The forms of therapeutic compositions include powder, liquid or aerosol formulations (col. 10, lines 30-36) that are not necessarily “colloidal” within the broadest meaning of the claims (claim 40).
With regard to claim-recited limitations “improving a microbiome imbalance” (claim 25) and “a respiratory disorder associated with microbiome dysbiosis” (claim 45): the cited document clearly teaches that bacterial extracts are effective to treat “respiratory infections”. Infections in a subject are “microbiome imbalance” and “microbiome dysbiosis” which are characterized by presence of harmful pathogens relative to a healthy state characterized by presence of health beneficial microbes. In view of as-filed specification term “microbiome imbalance” or “dysbiosis” refers to the state in which a system has an imbalance in beneficial and harmful microbes (par. 044 of published application). Thus, the cited method comprising administration of bacterial lysates is intended for treating the same conditions and/or disorder within the broadest reasonable meaning of the claims.
In particular, in the method of US 9,463,209 (Bauer et al) the bacterial extract is administered via the oral route (col. 10, lines 29 and 44). US 9,463,209 (Bauer et al) is silent about administration via intranasal route.
However, the prior art; for example: the cited reference by Rial teaches intranasal administration of alkaline bacterial extract derived from the same bacteria Moraxella catarrhalis, Haemophilus influenzae, Klebsiella pneumoniae and Staphylococcus sp. (as in the cited above US 9,463,209 (Bauer et al)) for treating or preventing respiratory disorders associated with inflammation or allergic conditions (abstract; page 748 at item 2.1 and at item 2.3). The cited reference by Rial explicitly recognizes that treatment with bacterial extract/lysate induces inflammation and results in full protection against pneumococcal pneumonia, which is a respiratory infection or lung infection. Thus, the therapeutic effect of the method of Rial relates to “improving a microbiome imbalance” and “a respiratory disorder associated with microbiome dysbiosis” within the broadest reasonable meaning of the claims.
Further, the cited reference by Kearny teaches that the alkaline bacterial extract known as OM-85 BV or Broncho-Vaxom, which is the same alkaline bacterial extract as disclosed by the cited US 9,463,209 (Bauer et al), can be administered orally, as it disclosed by the cited US 9,463,209 (Bauer et al), but it can be also administered intranasally (see Kearny at page 2, par. 2) for the benefit of activation of local mucosal immunity at the level of respiratory epithelium. The cited reference by Kearny acknowledges that bacterial lysate have ben used for treating respiratory infections (page 2, col.1, par. 3, first line), thereby, treating microbiome imbalance/dysbiosis associate with respiratory infections.
Furthermore, the reference by Ellis teaches that the intranasal route of delivery of vaccine based on attenuated or lysed bacteria confers superior clinical outcomes comparatively to oral route in applications for combating infections and allergic condition of respiratory tract (see abstract)
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to provide alkaline bacterial extract in the method US 9,463,209 (Bauer et al) via intranasal route with a reasonable expectation of success in treating or preventing respiratory disorders associated with infections or with microbiome imbalance/dysbiosis because therapeutic bacterial lysate preparations extracts are provided by intranasal route (Rial), because the bacterial lysate of US 9,463,209 (Bauer et al) has been taught or suggested to be provided by either oral or intranasal route (Kearny) and because an intranasal route of delivery of therapeutic bacterial preparations for respiratory disorders is considered to provide for superior clinical outcome versus oral delivery (Ellis).
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
With regard to clams 32-35: Optimization of doses and forms of therapeutic bacterial lysate preparations would be an obvious practice for one of skill in the art upon route experimentation depending of severity of conditions and within the ranges as taught and suggested by the cited prior art.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Claims 25, 27, 29, 30, 32-37 and 39-46 as amended are/remain rejected under 35 U.S.C. 103 as being unpatentable over US 9,463,209 (Bauer et al), Rial et al ( Microbes and Infection, 2016, 18, pages 747-757), Kearny et al (Ann Allergy Asthma Immunol. 2015, pages 1-6) and Ellis et al (“Comparative efficacy of intranasal and oral vaccines against Bordetella bronchiseptica in dogs”. The Veterinary Journal, 2016, 212, pages 71-77) as applied to claims 25, 27, 29, 30, 32-37 and 39-45 above, and further in view of Guani-Guerra et al (Archives of Medical Research., 2011, 42, pages 189-194).
The cited documents US 9,463,209 (Bauer et al), Rial et al, Kearny et al and Ellis et al as above. All cited documents teach administration of bacterial lysate-containing formulations in various forms including intranasal formulations for administration to subjects including humans.
As applied to new claim 46 the reference by Guani-Guerra et al further discloses and teaches that therapeutic bacterial lysate-containing formulations for intranasal administration to human subjects are routinely formulated with glycerol (entire document including page 190, col. 2, par. 3, last 3 lines) which is a permeation enhancer within the broadest meaning of the new claim 46 and in view of specification (par. 0073 of published application US 2022/0143111).
Therefore, it would have been obvious to one having ordinary skill in the art at the time the claimed invention was filed to provide immunomodulating bacterial lysate-containing intranasal formulations with permeation enhancers because it is a common and routine practice.
Thus, the claimed invention as a whole was clearly prima facie obvious, especially in the absence of evidence to the contrary.
The claimed subject matter fails to patentably distinguish over the state art as represented be the cited references. Therefore, the claims are properly rejected under 35 USC § 103.
Response to Arguments
Applicant's arguments and Declaration by Edouard Baulier filed on 10/01/2025 have been fully considered but they are not all found persuasive. The contents of declaration by Jacques Bauer filed on 6/25/2024 were revisited.
The rejection of claims 30 and 38 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, has been withdrawn in view of current claim amendment as drawn to forms suitable for intranasal or intratracheal routes of administration.
TD over claims of US 11,801,271 (Bauer et al) has been filed and approved. Thus, the rejection of claims on the ground of nonstatutory double patenting has been withdrawn. The pending claims remain broader then issued claims at least with regard to bacterial lysate.
With regard to claim rejection under 35 U.S.C. 103 as being unpatentable over US 9,463,209 (Bauer et al), Rial et al (Microbes and Infection, 2016, 18, pages 747-757), Kearny et al (Ann Allergy Asthma Immunol. 2015, pages 1-6) and Ellis et al (“Comparative efficacy of intranasal and oral vaccines against Bordetella bronchiseptica in dogs”. The Veterinary Journal, 2016, 212, pages 71-77) Applicants’ main arguments are directed to the ideas that the cited references in combination do not teach or suggest administration of claimed alkaline bacterial extract to humans by intranasal route and that the prior art teachings as based on mouse animal models can be extrapolated to humans.
The argument is not found persuasive because although the cited US 9,463,209 (Bauer et al) discloses administration of claimed alkaline bacterial extract to a mouse model, it clearly teaches and suggests equivalency of the alkaline bacterial extract beneficial effects in humans and in mammalian animal models in therapeutic applications (col. 4, lines 58-60; col. 35, lines 38-40; col. 38, lines 40-41).
Herein it is also noted that the contents of Declaration by Jacques Bauer and signed by Christian Pasquali filed on 6/25/2024 were revisited. In particular, the Declaration (see item 3) states that experiments based on mouse models do not correlate to human intranasal administration because a portion of drops delivered to a mouse nostril goes to the mouse gut (as shown by data of the figure 1 of the IDS reference by Southam filed on 6/25/2024). However, this statement and argument based thereon are not found persuasive because one of skill in the art would clearly and obviously make sure and take precautions for a proper delivery of drug into nostrils of animals and for avoiding drug wastes or spills. For example: the other reference by Rial (Infection and Immunity, 2004, Vol. 72, No. 5, pages 2679-2688), which is submitted by Applicants with response on 10/01/2025, clearly describes routine and conventional practice that, when drug is delivered into nostrils, the animals (mouse model) are kept in a vertical position for 1 min to ensure migration of drug into respiratory tract (see page 2680, col. 1, section “immunization model”). Thus, it would be obvious to one of skill in the art to practice routine and conventional techniques for proper drug delivery as intended for intranasal/intratracheal route of administration. Moreover, the as-filed instant specification examples are all based on mouse models; and, thus, there is no description of human model for practicing instant invention in order to support criticality of differences between mouse model and human model for nasal drug delivery as it is presently argued.
The Declaration by Edouard Baulier filed on 10/01/2025 also addresses the issue (see item 4) that that the prior art teachings (cited reference by Rial), as based on mouse animal models for administration of a bacterial extract by intranasal route, cannot be extrapolated to humans because of applicants’ unexpected results about efficiency of a low dose of the bacterial extract. This argument is not found persuasive for the very least reason that the low doses as argued in Declaration are shown in volumes; and, thus, the amounts or concentrations of active ingredients for unexpected effects cannot be delineated.
With regard to the cited reference by Kearny Applicants appear to argue (response page 7) that the cited particular teaching about administration of bacterial lysate by oral or nasal route refers to a generic bacterial lysate but not to the claimed bacterial extract or to OM-85 BV product. Upon review it is not found true or persuasive. The cited reference by Kearny (see page 2, col. 1, par. 2) clearly teaches and/or suggest that the bacterial lysates can be administered orally or intranasally; and the list of bacterial species in the bacterial lysate comprises the same bacteria as claimed. Please, note that the claimed “bacterial extract” does not necessarily contain all claim-recited bacterial species but only a selection of at least one by the virtue of language “Gram-positive or Gram-negative bacterial species are chosen from …” .
Some of Applicants’ arguments (response pages 8-9) are drawn to the use of unexpectedly low doses of bacterial lysate (1 mg) for nasal administration to achieve excellent efficiency as shown in specification examples when compared to the prior art oral administration dose 3.5-7 mg (published application par. 0040).This argument is not found particularly convincing since 1 mg is administered to mice and dose 3.5-7mg is administered to human. Clearly, a larger dose would be administered to larger mammalians.
Some of Applicants’ arguments and Declaration (item 3) are drawn to the effects of administration of bacterial extract on the gut microbiome when administered intranasally. Yet, the claimed method is not limited to microbiome imbalance or dysbiosis in the gut. Moreover, the specification appears to recognize that increase of Lactobacillus in gut upon intranasal administration of bacterial extract leads to improvement in immunity, thus, tolerance towards pathogens. The prior art recognizes immunity improvement upon intranasal admisnitriaotn of bacterial extract (Kearny, Guani-Guerra).
No claims are allowed.
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.
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Vera Afremova
January 28, 2026
/VERA AFREMOVA/ Primary Examiner, Art Unit 1653