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 .
Amendments Received
Amendments to the claims were received and entered on 09/22/2025.
Status of Claims
Claims 11 and 13 have been cancelled, and claim 21 has been newly added.
Claims 1-10, 12, and 14-21 are currently pending.
Claims 1-6 and 10, 12, and 14-21 are under consideration, as claims 7-9 are withdrawn.
Priority
The present application claims status as a 371 (National Stage) of PCT/IB2020/060626 filed on November 11, 2020 and claims priority to Italian application IT102019000020805 filed on November 11, 2019. Acknowledgment is made of applicant’s claim for foreign priority and papers submitted under 35 U.S.C. 119 (a)-(d). The present application and all claims are being examined with an effective filing date of 11/11/2019. In future actions, the effective filing date may change due to amendments or further review of priority documents.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/22/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections
In view of Applicant’s amendments, objections to claims 6 and 19-20 are hereby withdrawn.
Withdrawn Rejections
In view of Applicant’s cancellation of claims 11 and 13, all rejections of claims 11 and 13 are now moot and are hereby withdrawn.
In view of Applicant’s amendments, rejections of claims 1-6 and 10, 12, and 14-18 under 35 USC § 112(b) are hereby withdrawn.
In view of Applicant’s amendments, rejection of claim 5 under 35 USC § 112(b) is hereby withdrawn.
Maintained/Modified Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-6 and 10, 12, and 14-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
It is noted that MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow.'' Instant claims 1, 5, 10, 12, and 21 have been broadly interpreted to encompass a (composition comprising) genus of bacteria, coated with a genus of one or more (unlimited) lipids having crystalline structure in lamellar configuration, and (in the case of instant claim 21) further comprising a genus of food-grade, pharmaceutical or cosmetic additives and/or excipients. Instant claim 2 has been broadly interpreted to encompass a genus bacteria according to claim 1, wherein the at least one lipid is selected from a genus of mono-, di- or tri- glycerols esterified with saturated or unsaturated fatty acids, free saturated fatty acids, free unsaturated fatty acids, mono-alcohols esterified with saturated or unsaturated fatty acids, di-alcohols esterified with saturated or unsaturated fatty acids, and sucrose fatty acid esters (sucresters), wherein said saturated or unsaturated fatty acids, free or esterified with glycerol or mono- alcohols or di-alcohols or sucrose, have a number of carbon atoms comprised in the a range from C6 to C32. Instant claim 3 has been broadly interpreted to encompass a genus bacteria according to claim 2, wherein said at least one lipid comprises at least one lipid from a genus of mono-, di- or tri- glycerols esterified with saturated or unsaturated fatty acids; and at least one second lipid, wherein said second lipid is a genus of sucrose fatty acid esters, wherein said fatty acids esterified with the glycerol or with the sucrose have a number of carbon atoms comprised in the a range from C6 to C32. Instant claim 14 has been broadly interpreted to encompass a genus bacteria according to claim 2, wherein the at least one lipid is a genus of mono-alcohols esterified with saturated fatty acids. Instant claim 15 has been broadly interpreted to encompass a genus bacteria according to claim 2, wherein the at least one lipid is a genus of sucrose fatty acid esters comprising a mixture of mono-, di- and/or tri- sucrose fatty acid esters. Instant claim 16 has been broadly interpreted to encompass a genus of saturated or unsaturated fatty acids, free or esterified with glycerol, mono-alcohols, di-alcohols, or sucrose according to claim 2, wherein the fatty acids have a number of carbon atoms in the range of C14 to C24. It is noted that while Instant claims 4, 17, and 18 have been broadly interpreted to encompass a genus bacteria according to claim 1 in different proportions of bacterial cell content to lipid coating content, by weight. Instant claims 6, 19, and 20 have been broadly interpreted as encompassing a composition comprising a genus bacteria according to claim 1, having various concentrations in AFU/g.
MPEP 2163 I. states that to “satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.
MPEP 2163. II.A.3.(a) states that “Possession may be shown in many ways. For example, possession may be shown by describing an actual reduction to practice of the claimed invention. Possession may also be shown by a clear depiction of the invention in detailed drawings or in structural chemical formulas which permit a person skilled in the art to clearly recognize that inventor had possession of the claimed invention. An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention.
According to MPEP 2163.II.A.3.(a).ii), “Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’"
The specification is limited to characterization of a specific strain of bacteria L. rhamnosus in the form of granules obtained by subjecting said bacteria to a specific coating mix and lipids, specifically a commercial preparation “Biogapress Vegetal E471” (pg. 21, Experimental Part 1 and pg. 28, Experimental Part 2). Thus, all bacteria may not be amenable to such manipulations. There is no disclosure of any particular structure to function/activity relationship in the disclosed species of any of the recited bacteria. The specification fails to describe sufficient representative species of these bacteria by any identifying structural characteristics or properties, for which no predictability of structure is apparent. One skilled in the art therefore cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus. In addition, the specification is likewise limited to characterization of a single lipid species, mono- and di-glycerides of C16–C18 fatty acids from the commercial preparation E471, and does not disclose sufficient representative species of the claimed genus of lipids (including free saturated or unsaturated fatty acids, mono- and di-alcohol esters, or sucrose fatty acid esters), nor does it establish any structure–function correlation demonstrating that these widely variant lipid species are capable of forming the claimed multilayer crystalline lamellar coating. Accordingly, while claim 16 narrows the carbon-chain length relative to claim 2, the specification still discloses only a single lipid species—mono- and di-glycerides of C16–C18 fatty acids (commercial E471)—and does not provide additional representative species or an identifying structure-function correlation demonstrating possession of the broader genus.
While MPEP 2163 acknowledges that in certain situations “one species adequately supports a genus,” it also acknowledges that “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus.” In view of the widely variant species encompassed by the genus, the examples described above is not enough and does not constitute a representative number of species to describe the whole genus. Therefore, the specification fails to describe a representative species of the claimed genus. Given this lack of additional representative species as encompassed by the claims, Applicants have failed to sufficiently describe the claimed invention, in such full, clear, concise, and exact terms that a skilled artisan would recognize applicants were in possession of the claimed invention.
Response to Arguments for Rejections under 35 USC § 112(a)
Applicant’s arguments in the response filed on September 22, 2025 have been fully considered, including the assertion that a person of ordinary skill in the art “would know exactly what to do” to obtain a multilayer crystalline lamellar lipid coating on any of the listed bacterial species based on the present disclosure. The examiner agrees that terms such as “lamellar,” “crystalline,” and “multilayer crystalline lamellar configuration” are structural descriptors understood in the lipid-coating arts. However, written description requires more than recitation of a known structural term. It requires disclosure demonstrating possession of all embodiments falling within the full scope of the claimed genus.
In the instant case, the specification as filed demonstrates possession of a single exemplified embodiment: granulation and lipid-coating of L. rhamnosus using a specific mono/diglyceride mixture (E471) under defined process conditions, and may reasonably support embodiments closely related to those disclosed (e.g., other Lactobacillus species or closely related probiotic bacteria having similar cell-wall composition, and lipid compositions structurally similar to the disclosed mono- and diglycerides of C16–C18 fatty acids). However, the specification does not provide identifying characteristics, comparative data, or structural-functional reasoning sufficient to establish that the claimed multilayer crystalline lamellar lipid architecture would be achieved for the numerous additional bacterial genera and lipid classes broadly recited in the claims. Listing species and lipid categories, without more, does not demonstrate possession of the full scope of the genus. Pursuant to MPEP 2163 I. A., a "laundry list" disclosure of every possible moiety does not necessarily constitute a written description of every species in a genus because it would not "reasonably lead" those skilled in the art to any particular species
Applicant’s reliance on the general steps of granulation, coating, and tempering does not cure the written-description deficiency. While the meaning of “lamellar crystalline structure” is understood, the specification does not describe how the inventors achieve this structure across diverse bacterial species with differing surface chemistries, moisture content, and cell-wall compositions, nor across lipid systems substantially broader than the specific mono/diglyceride mixture disclosed. Absent identifying structural characteristics or a demonstrated rationale showing that all claimed bacteria and all claimed lipids will form the same multilayer crystalline lamellar architecture under the disclosed process, the specification fails to establish possession of the full breadth of the genus now claimed.
Accordingly, Applicant’s arguments do not overcome the written-description rejection, and the rejection under 35 U.S.C. §112(a) is maintained.
Claim Rejections - 35 USC § 103
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.
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.
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.
Claims 1-5, 10, 12, and 14-18 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Mogna, G. and Mogna, L. (US20140370107A1, herein “Mogna”, cited in the IDS), Marino et al. (Potential application of monoglyceride structured emulsions as delivery systems of probiotic bacteria in reduced saturated fat ice cream, LWT-Food Science and Tech, Vol 96, Oct 2018, pg. 329-334, cited in a previous office action) and Sasaki et al. (JPH0787950A, English translation relied upon, cited in the IDS).
Regarding claims 1, 5, 10, 12 and 21, Mogna teaches a multilayer coated or microencapsulated bacteria, which can be in powder, granular, dehydrated powder or lyophilized form, wherein said bacteria are coated with a coating material comprising, or alternatively, consisting of at least one lipid (Specification, pg. 2-3, para 0016 and 0037). Mogna further teaches that the coated bacteria “are coated or microencapsulated (covered) with a coating comprising or, alternatively, consisting of at least one lipid of vegetable origin. Said coating is a multilayer coating formed of a number of coating layers “n” comprised from 2 to 10. When n=2, the first and the second coating layer comprise or, alternatively, consist of a lipid of vegetable origin which is the same between them; or else when n=2, the first and second coating layer comprise or, alternatively, consist of a lipid of vegetable origin which differs between them” (pg. 4, para 0051). Furthermore, Mogna teaches the addition of the coated bacteria, the “finished product”, to a food product “selected from the group comprising milk, whole fresh milk, partially skimmed milk, powdered or freeze-dried milk, cheese, fresh cheese, aged cheese, grated cheese, butter, margarine, yogurt, cream, milk- and chocolate-based” (pg. 3, para 0040). Mogna’s disclosure of coated bacterial granules added to food products inherently teaches a composition comprising the granules together with a food-grade additive or excipient, thereby rendering both claims 5 and 21 obvious. Mogna teaches the stability and resistance to gastric juices, pancreatic juices and bile salts in said bacteria (pg. 5, para 0068-0099). It is noted that claim 10 is directed to granular bacteria obtained by the process of claim 7, wherein claim 7 is directed to a process for preparing the bacteria of claim 1. Therefore, claim 10 is being interpreted as being directed to the granular bacteria of claim 1. The limitation that requires making the granular bacteria by using the process of claim 7 is a product by process limitation that is given little patentable weight because determination of patentability is based on the characteristics of the product itself. Pursuant to MPEP 2113, "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production.” Furthermore, "[b]ecause validity is determined based on the requirements of patentability, a patent is invalid if a product made by the process recited in a product-by-process claim is anticipated by or obvious from prior art products, even if those prior art products are made by different processes." Amgen Inc. v. F. Hoffmann-La Roche Ltd., 580 F.3d 1340, 1370 n 14, 92 USPQ2d 1289, 1312, n 14 (Fed. Cir. 2009). See also Purdue Pharma v. Epic Pharma, 811 F.3d 1345, 117 USPQ2d 1733 (Fed. Cir. 2016).
Mogna does not expressly teach wherein said lipid has a lamellar configuration with a crystalline structure.
Marino et al. teaches a saturated monoglyceride structured emulsion (MSE) containing a probiotic Lactobacillus rhamnosus strain, investigating the potential of MSE as a delivery system for said probiotic in ice cream. Marino et al. teaches “it was concluded that the monoglyceride crystalline structures formed in the MSE played both probiotic protective and structuring role” (Abstract). Briefly, L. rhamnosus was added as a fresh pellet (1 mL in 100 g of MSEs). No viability loss was observed as a consequence of emulsion preparation. L. rhamnosus “entrapped in MSE” was added to ice cream, as were free cells, prior to “wipping/freezing phase”. Physiochemical analyses and viable count was performed. Results indicated that “in the probiotic entrapped in MSE the survival of cultures during mix freezing resulted improved (p < 0.05) in comparison to the control and ice cream containing free cells of L. rhamnosus”. Marino et al. further teach that “the presence of monoglyceride crystalline lamellar bilayers preventing oil spreading by the generation of a network conferring to ice cream a good resistance to meltdown and structural collapse”. Marino et al. concludes that the results “confirm the ability of MG lamellar structures to protect bacteria cells”.
With respect to applicant amending claim 1 to recite that the lipid-coating matrix comprises at least one lipid “in a multilayer crystalline lamellar configuration forming a crystalline laminar structure”, this amendment does not overcome the rejection. As noted above, Mogna expressly teaches multilayer lipid coatings over probiotic granules, and Marino teaches that saturated monoglycerides form lamellar crystalline structures that protect L. rhamnosus. A person of ordinary skill in the art would have found it obvious to incorporate the lamellar crystalline lipid phases disclosed in Marino into Mogna’s multilayer lipid-coating system to enhance bacterial stability. Accordingly, the amended limitation remains taught or suggested by the cited art.
An invention would have been obvious to a person of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, the teachings of Marino et al., that a crystalline structure comprising a lipid in a lamellar configuration is protective to the bacteria it contains, would have led said practitioner to modify the coated and microencapsulated bacteria of Mogna so that the lipid of the coating material is selected or modified such that is a lipid of crystalline structure with lamellar configuration. Given that Marino et al. discloses a monoglyceride structured emulsion containing a probiotic that demonstrated improved viability against various stressors such as freezing, as compared to free cells, said practitioner would have readily predicted and would have a reasonable expectation of success that the combination of teachings would successfully result in the granular bacteria gastroprotected with a coating matrix, according to instant claim 1. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claims 2 and 14-16, Mogna teaches wherein the lipid of the coating material comprises saturated vegetable fats selected from the group comprising mono- and di-glycerides of saturated fatty acids, polyglycerols esterified with saturated fatty acids and free saturated fatty acids, wherein the saturated fatty acids comprise 8 to 32 carbon atoms, even more preferably 16 to 24 carbon atoms (pg. 3, para 0041-0043). Mogna does not teach wherein the lipid of the coating material comprises mono-alcohols esterified with saturated fatty acids (i.e., wax esters) or mixtures of mono-, di- and/or tri- sucrose fatty acid esters.
Sasaki et al. teaches a double coated particle, wherein the primary coating membrane consisting of a granular or powdery core substance, a continuous layer of lipid covering the surface of the core substance…a secondary coating film comprising an adherent layer of the lipid powder described above…having a melting point of 40°C or higher” (pg. 3, para 0010). Sasaki et al. teaches the core substance that consists of a granular or powdery substance may be bacteria (pg. 3, para 0011). Sasaki et al. further teaches regarding the lipid that can be used as the primary coating agent, “such lipids include naturally obtained animal and vegetable oils…fatty acid monoglycerides, fatty acid diglycerides, propylene glycol fatty acid esters, sucrose fatty acid esters, fatty acids, higher alcohols, waxes, phosphorus or nitrogen containing phospholipids, glycolipids having sugar constituents, sulfolipids having sulfonic acid groups, sterols, hydrocarbons, and hydrogenates products thereof. One or two or more of them can be used” (pg. 4, para 0012). It is noted that “waxes” contain wax esters, and thereby satisfies the claim limitation of “mono alcohols esterified with saturated fatty acids, as recited in claim 14. Sasaki et al. teaches the double coated particles for imparting “excellent acid resistance” and “high survival rate” (pg. 9, para 0036). Both Mogna and Sasaki et al. teach at least a lipid coated granular bacteria, wherein the at least one lipid may be fatty acid mono- and diglycerides. Given that both Mogna and Sasaki et al. are using the same materials for the same purpose (i.e., conferring protection and thereby increased survival to bacterial cells), it would be obvious for a person of ordinary skill in the art, to substitute the lipid coated layer of Mogna (e.g., mono- and di-glycerides of saturated fatty acids) with the sucrose fatty acid ester or wax(es) taught by Sasaki et al., wherein the sucrose fatty acid esters comprise mixtures of at least mono- and di- sucrose fatty acid esters, and expect predictable results (see MPEP 2144.06, “Substituting equivalents known for the same purpose”).
Regarding claim 3, as described above, Mogna teaches multilayered lipid coated granular bacteria, wherein the lipid coating may be the same or different lipids. Mogna teaches lipids that can be used for the coating material, such as polyglycerols esterified with saturated fatty acids and free saturated fatty acids having a range of 6 carbons to 32 carbon atoms. Mogna does not however teach sucrose fatty acid esters.
Sasaki et al. teaches a double coated particle, wherein the primary coating membrane consisting of a granular or powdery core substance, a continuous layer of lipid covering the surface of the core substance…a secondary coating film comprising an adherent layer of the lipid powder described above…having a melting point of 40°C or higher” (pg. 3, para 0010). Sasaki et al. teaches the core substance that consists of a granular or powdery substance may be bacteria (pg. 3, para 0011). Sasaki et al. further teaches regarding the lipid that can be used as the primary coating agent, “such lipids include naturally obtained animal and vegetable oils…fatty acid monoglycerides, fatty acid diglycerides, propylene glycol fatty acid esters, sucrose fatty acid esters, fatty acids, higher alcohols, waxes, phosphorus or nitrogen containing phospholipids, glycolipids having sugar constituents, sulfolipids having sulfonic acid groups, sterols, hydrocarbons, and hydrogenates products thereof. One of two or more of them can be used” (pg. 4, para 0012). Regarding the secondary coating agent, Sasaki et al. teaches, “such lipids include naturally obtained animal and vegetable oils…fatty acid monoglycerides, fatty acid diglycerides, propylene glycol fatty acid esters, sucrose fatty acid esters, fatty acids, higher alcohols, waxes, phosphorus or nitrogen containing phospholipids, glycolipids having sugar constituents, sulfolipids having sulfonic acid groups, sterols, hydrocarbons, and hydrogenates products thereof. One of two or more of them can be used” (pg. 4, para 0012). Sasaki et al. teaches the above described double coated particles for imparting “excellent acid resistance” and “high survival rate” (pg. 9, para 0036). Both Mogna and Sasaki et al. teach double lipid coated granular bacteria, wherein the lipids used for the coatings are different, wherein one lipid may be fatty acid mono- and diglycerides. Given that both Mogna and Sasaki et al. are using the same materials for the same purpose (i.e., conferring protection and thereby increased survival to bacterial cells), it would be obvious for a person of ordinary skill in the art, to substitute the second lipid coated layer of Mogna with the sucrose fatty acid ester taught by Sasaki et al. and expect predictable results (see MPEP 2144.06, “Substituting equivalents known for the same purpose”).
Regarding claims 4, and 17-18, Mogna teaches, with respect to the coated or microencapsulated bacteria described above, “a given amount “X” by weight of bacteria, having a concentration expressed in CFU/g, is coated or microencapsulated with a given amount “Y” by weight of a coating material comprising lipids of vegetable origin. The amount by weight can be less than, equal to or greater than X. The ratio by weight Y:X, relative to the final weight of the coated bacteria, can be, for example, 1:1, or 1.25:1, or 1.50:1, or 1.75:1, or 2:1” (pg. 2, para 0022). Mogna discloses an example wherein 100 grams of coating material is applied to 200 grams of bacteria (pg. para 0025), equating to approximately 67% by weight of bacteria and 33% by weight of lipid coating material, with respect to the total weight of the coated bacteria. Pursuant to MPEP 2144.05 II.,“Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claims 6 and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Mogna and Marino et al., as applied to claims 1 and 5 above, further in view of Singh et al. (Rapid Quantification of the Total Viable Bacterial Population on Human Hands Using Flow Cytometry with SYBR® Green I. Cytometry Part B, Sept 2019; 96B: 397–403, cited in a previous office action).
The combined teachings of Mogna and Marino et al. as they apply to claims 1 and 5 have been detailed above. Briefly, Mogna teaches a multilayer lipid coated or microencapsulated granular bacteria, added to a food product such as yogurt or milk. Marino et al. teaches that lipid coating material that crystalline structures in lamellar configuration imparts superior qualities for preservation and protection of the encased bacteria. Combined. Mogna and Marino et al. teach a food product comprising granular bacteria that is coated with lipid material that is of crystalline structure and in lamellar configuration. Neither Mogna or Marino et al. teach concentrations of said bacteria in active fluorescent units (and the values recited in claims 6, 19 and 20).
Regarding claims 6, and 19-20, Mogna teaches concentrations of bacteria measured in colony forming units, which is well known and widely employed by persons of ordinary skill in the art for enumerating bacteria. In the samples disclosed in Mogna, the concentration of Lactobacillus rhamnosus is 5x10⁹ CFU/10 ml (pg. 5, para 0073). Regarding active fluorescent units, the instant specification states that it (AFU) “is measured using the flow cytometry method as defined in the present invention and it refers to bacteria with integral cell membrane on one gram of composition”.
Singh et al. teaches that “traditional detection of bacteria is typically performed by standard culture-based counting on solid agar or using most probable number (MPN)liquid methods. Examples of these include, for colony-forming units (CFU) detection…” and that although they may be simple to perform, “a major limitation is the possibility of the presence of dormant, live, inactive, damaged, or viable but non-culturable (VBNC) bacterial cells in the sample” (pg. 398, left column, top). Singh et al. further teaches an alternative approach and solution is to use the flow cytometry method, which allows for rapid differentiation and quantification of live and dead bacteria (pg. 398, left, bottom). Singh et al. disclose the method using hand wash samples; “total (both live and dead) and live bacterial populations were analyzed using SYBR® Green I (SG) and PI staining(Fig. 1). SG stained all bacterial cells irrespective of mem-brane damage or the viable but non culturable nature of bacterial cells (Fig. 1A), whereas PI stained only severely damaged and dead cells. SG stained cells provided a total count of all bacterial cells present in the samples irrespective of the status of viability. Thus, bacterial cells that co-stained with SGPI were shifted out of the bacterial cell gate (Fig. 1B). Hence, in the presence of PI, the same gate that was used to determine the total bacterial cell concentration (Fig. 1A) now included only viable, intact bacteria(Fig. 1B) (14)” (pg. 399 Fig. 1 and pg. 400, right column, top para). Singh et al. conclude that the flow cytometry method “was the only method that could detect both live and dead bacterial cells and allowed for the detection of any unculturable bacteria, based on the uptake of dyes” (pg. 402, right column, “Conclusion”). Therefore, for the reasons outlined by Singh et al., namely ensuring a more accurate count of viable bacteria, the flow cytometry method offers an obvious advantage to plate-counting, especially in the context of concentration of bacteria in a food product. With respect to the exact concentration (AFU/g) recited in the claims, pursuant to MPEP 2144.05, 11., “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. The concentration of the granular bacteria in the composition (food product) is clearly a result specific parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ. It would have been customary for an artisan of ordinary skill to determine the optimal concentration of the granular bacteria in the composition needed to achieve the desired results. Thus, an ordinary skilled artisan would have been motivated to modify the concentration of the bacteria taught by Mogna, based on the more accurate viable bacterial count using the flow cytometry method taught by Singh et al., and provide a concentration of active fluorescent units per gram of composition.
An invention would have been obvious to a person of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, the teachings of Singh et al., that the traditional plate counting method is less accurate than the flow cytometry method when counting viable bacteria and is a faster process, would have motivated said practitioner to modify the method of Mogna, and used the flow cytometry method to determine active fluorescents unit per gram of composition. Given that Singh et al. demonstrates a successful method of differentiating and quantifying live and dead bacteria, said practitioner would have readily predicted and had a reasonable expectation of success that the combination of teachings would successfully result in a composition comprising the granular bacteria according to claim 1 in various concentrations of AFU/g. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Response to Arguments for Rejections under 35 USC § 103
In the response filed on September 22, 2025, applicant argues, in summary, that: (i) Mogna, Marino, and Sasaki operate in “incompatible systems” such that their teachings cannot be combined; (ii) Marino’s disclosure of lamellar monoglyceride crystalline structures is limited to hydrated emulsions and therefore cannot reasonably be applied to Mogna’s lipid-coated bacterial granules; (iii) Sasaki purportedly teaches a coating process fundamentally distinct from Mogna’s, rendering sucrose esters and wax esters “unsuitable” substitutes; and (iv) the amendments to claim 1 remove the cited prior-art teachings. Applicant’s arguments have been fully considered but have not been found persuasive for the reasons set forth below.
Applicant’s arguments regarding Mogna - Applicant argues that Mogna teaches a “dry lipid encapsulation” system that is allegedly incompatible with the hydrated or emulsion-based systems of other references. However, the rejection does not rely on Marino or Sasaki for any process steps. Mogna is relied upon solely for its teaching of multilayer lipid coatings over probiotic bacterial granules. Mogna expressly discloses that such multilayer lipid coatings are used to stabilize probiotic bacteria during storage and gastrointestinal passage. This teaching squarely applies to the claimed multilayer lipid-coating matrix. Applicant’s argument that Mogna “cannot” be combined with other references because of differences in preparation conditions is not persuasive. Under long-standing case law, differences in preparation environment do not preclude combining references unless the prior art explicitly teaches away or unless the modification would render the primary reference unsuitable for its intended purpose. Pursuant to MPEP 2141.02, VI., "the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). Applicant identifies no such teaching. Mogna’s underlying principle—stabilizing bacteria using lipid multilayers—is wholly retained in the combination.
Applicant’s arguments regarding Marino - Applicant devotes substantial discussion to the fact that Marino’s lamellar monoglyceride (MG) crystalline phases were demonstrated within a hydrated emulsion matrix, and contends that such lamellar structures are “incompatible” with Mogna’s dry lipid system. Applicant further argues that Marino’s bacteria reside in “aqueous domains” and therefore cannot suggest a lipid coating. However, these arguments mischaracterize both Marino and the basis of the rejection.
The rejection relies on Marino for the structural and functional properties of lamellar MG crystalline phases, not for its process. Marino teaches that saturated monoglycerides form multilayer lamellar crystalline domains that protect L. rhamnosus by stabilizing the bacterial surface interfaces within the lipid phase. This is a structural teaching, not one dependent upon the specific food-emulsion environment in which Marino demonstrated the result. Applicant identifies no statement in Marino that the lamellar crystalline structure exists only in hydrated emulsions, ceases to exist in dry lipid systems, requires an aqueous continuous phase, or is incompatible with lipid coatings.
Lamellar crystalline MG phases are known to form in both hydrated and anhydrous lipid matrices. Applicant’s argument rests on the premise that Marino’s lamellar crystalline structures can only form in hydrated systems. Applicant identifies no evidence or disclosure to support such a limitation. As explained above, the rejection does not rely on Marino’s emulsion-processing environment but on the structural and function teaching that saturated monoglycerides form lamellar crystalline phases that provide bacterial protection. The relevant teaching in Marino is the property of the lamellar MG crystalline phase, not the specific aqueous medium in which Marino demonstrated it. In contrast, the lipid-science literature establishes that saturated monoglycerides are known to produce lamellar phases in anhydrous and semi-solid lipid systems as well, because formation is governed primarily by fatty-acid chain packing and temperature, not on hydration level. Marino does not limit its teaching to hydrated systems, nor does it discourage applying lamellar crystalline lipid phases in other lipid matrices. Therefore, the fact that Marino conducted its demonstration in a hydrated emulsion does not restrict the teaching that lamellar MG crystalline structures protect bacteria.
Applicant’s “different systems” argument does not amount to teaching away. A reference teaches away only when it expressly discourages applying the teaching in the manner proposed. Applicant identifies no disclosure in Marino that discourages the use of lamellar MG crystalline structures in lipid coatings or dry systems. The argument therefore cannot constitute teaching away.
Applicant’s arguments regarding Sasaki - Applicant asserts that Sasaki’s use of molten lipid deposited over powders is incompatible with Mogna’s fluid-bed coating process. Again, this mischaracterizes the rejection.
Sasaki is not relied upon for process steps. Sasaki is cited solely for the disclosure of sucrose fatty-acid esters, wax esters, fatty-acid esters, and other known lipid-coating materials as suitable for protecting bacterial or sensitive bioactive cores. These lipids are well-established equivalents to the glycerides taught in Mogna. Applicant provides no evidence that these lipids cannot form crystalline structures, cannot form multilayers, or cannot be used in the lipid-coating art outside Sasaki’s specific process.
Process differences do not negate substitutable lipid species. Under MPEP 2144.06, substitution of a known lipid (sucrose ester, wax ester, fatty-acid ester) for a similar lipid, for the same purpose, in a known lipid-coating system is prima facie obvious absent a teaching away or evidence of unexpected results. Applicant provides neither.
No statement in Sasaki limits the lipid species to the exact process conditions described therein. Applicant’s argument rests entirely on the fact that Sasaki’s lipid is applied in a particular manner. This does not negate the teaching that sucrose esters and wax esters are suitable coating lipids. Accordingly, Sasaki remains properly combinable with Mogna.
Applicant’s arguments regarding Singh - Applicant argues that Singh’s AFU measurements are “not comparable” to Mogna’s CFU measurements. The rejection acknowledges this distinction and relies on Singh only to illustrate that AFU/CFU variations occur in the probiotic art and that adjustment of viable-cell counts is a matter of routine optimization. Applicant does not dispute that determining viable AFU/g in a composition is a routine analytical step within the art. Applicant also does not allege unexpected results tied to the specific AFU ranges recited. Thus, Singh remains appropriate for supplying the rationale that viability-count parameters constitute routine optimization.
Applicant’s arguments regarding the amended claim 1 - Applicant argues that amendments to claim 1, specifically adding “multilayer crystalline lamellar configuration forming a crystalline laminar structure”, render the applied art inapplicable. This argument is not persuasive. As clarified herein, Mogna continues to teach multilayer lipid coatings for bacteria and Marino teaches that saturated monoglycerides form lamellar crystalline structures that protect L. rhamnosus. The combination therefore teaches the claimed multilayer + crystalline + lamellar lipid-coating matrix. Accordingly, the amendments do not overcome the rejection of claim 1.
Applicant’s argument have been considered in full but are not persuasive. The cited references continue to teach or suggest each and every limitation of the instant claims, including claim 1 as amended. Therefore, the rejections of claims 1-6 and 10, 12, and 14-21 under 35 USC 103 are maintained, as outlined above.
Conclusion
No claim is in condition for allowance.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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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/NAGHMEH NINA MOAZZAMI/Examiner, Art Unit 1652
/ROBERT B MONDESI/Supervisory Patent Examiner, Art Unit 1652