DETAILED CORRESPONDENCE
Status of the Application
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 4, 2026 has been entered.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1, 3-10, 13, 14, 19, and 22-29 are pending in the application and are being examined on the merits.
Applicant’s amendment to the claims, filed May 4, 2026, is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed May 4, 2026 in response to the final rejection filed February 2, 2026 and the advisory action filed April 9, 2026 have been fully considered.
Claims 20 and 21 are canceled by applicant’s amendment filed May 4, 2026 and rejections previously applied to these claims are withdrawn.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on May 4, 2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDS is being considered by the examiner.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 1, 3-10, 13, 14, and 19 under 35 U.S.C. 112(b) as being indefinite in the recitation of “stable viability” in claims 1 and 19 is withdrawn in view of applicant’s amendments to recite “retains viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.” Given a broadest reasonable interpretation, the recitation of “retains viability for at least six months when stored at room temperature” is interpreted as meaning at least one microorganism cell is viable for at least six months when stored at room temperature.
Claim Rejections - 35 USC § 112(a)
The rejections of claims 1, 3-10, 13, 14, and 19 under 35 U.S.C. 112(a) as failing to comply with the written description requirement for the recitation of “a residual water content of from 3% to 14%” and “exhibits stable viability for at least six months if stored at room temperature” are withdrawn in view of applicant’s amendments to claims 1 and 19 to recite “a residual water content of from 3% to 14%” and to delete the phrase “exhibits stable viability for at least six months if stored at room temperature.”
Claims 1, 3-10, 13, 14, 19, and 22-29 are newly rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims”. See also MPEP 714.02. MPEP § 2163.II.A.3.(b) further states, “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, para. 1, as lacking adequate written description”. According to MPEP § 2163.I.B, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure” and “The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117”.
Claims 1 (claims 3-10, 13, 14, 22, 24, 26, and 28 dependent therefrom) and 19 (claims 23, 25, 27, and 29 dependent therefrom) have been amended to recite the limitation “wherein the microorganism component of the microorganism loaded multiphase biomaterial comprising nanocellulose retains viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.” Applicant’s instant remarks fail to show support for this limitation and there is no apparent descriptive support for this limitation in the original application. Consequently, the applicant’s amendment introduces new matter into the claims.
Claims 26 and 27 are newly rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
MPEP § 2163.II.A.3.(b) states, “when filing an amendment an applicant should show support in the original disclosure for new or amended claims”. See also MPEP 714.02. MPEP § 2163.II.A.3.(b) further states, “[i]f the originally filed disclosure does not provide support for each claim limitation, or if an element which applicant describes as essential or critical is not claimed, a new or amended claim must be rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112, para. 1, as lacking adequate written description”. According to MPEP § 2163.I.B, “While there is no in haec verba requirement, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure” and “The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117”.
New claims 26 and 27 recite the limitation “a humidity-impermeable aluminum composite foil.” The original application provides descriptive support for an “almost water-/humidity impermeable material. The packaging material for the packaging foil is an aluminum compound foil…” (specification at p. 24, lines 16-17). However, there is no apparent descriptive support for the limitation “a humidity-impermeable aluminum composite foil” in the original application. Consequently, the applicant’s amendment introduces new matter into the claims.
Claim Rejections - 35 USC § 103
Claims 1, 3-10, 13, 14, 22, 24, 26, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong et al. (CN102031248A; cited on Form PTO-892 mailed August 15, 2024; hereafter “Zhong-1”; reference is made to a machine translation filed August 15, 2024) in view of
Hessler et al. (US 2013/0004784 A1; cited on Form PTO-892 mailed August 15, 2024; hereafter “Hessler”),
Zhong et al. (CN102226174A; cited on Form PTO-892 mailed January 29, 2025; hereafter “Zhong-2”; reference is made to a machine translation filed January 29, 2025),
Spigelman et al. (US 2008/0107699 A1; cited on Form PTO-892 mailed on January 29, 2025; hereafter “Spigelman”),
Fischer et al. (US 2014/0284522 A1; cited on Form PTO-892 mailed on August 15, 2024; hereafter “Fischer”), and
Wang et al. (Int. J. Food Microbiol. 93:209-217, 2004; cited on Form PTO-892 mailed September 26, 2025; hereafter “Wang”).
This rejection has been modified from its previous version in order to address applicant’s amendments to the claims.
As amended, the claims are drawn to a method for making a microorganism loaded multiphase biomaterial comprising nanocellulose, the method comprising:
synthesizing a nanocellulose (BNC) multiphase biomaterial;
resuspending the microorganism in a buffer or a culture medium, and
loading the microorganism into and/or onto the nanocellulose multiphase biomaterial by spraying the microorganism onto the multiphase biomaterial,
wherein the microorganism is at least one selected from the group consisting of Lactococcus lactis, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus fermentum, Bacillus subtilis, and Bacillus megaterium;
incubating the loaded nanocellulose multiphase biomaterial with a moisture binder for drying, wherein the moisture binder is an osmotically and/or hygroscopically effective moisture-binding solution having a concentration of osmotically active and/or hygroscopic substances of 5 to 20%; and
freeze drying the nanocellulose multiphase biomaterial treated with moisture binder for 1-6 days to a residual water content of from 3% to 14%;
to thereby provide the microorganism loaded multiphase biomaterial comprising nanocellulose;
wherein the microorganism component of the microorganism loaded multiphase biomaterial comprising nanocellulose retains viability for at least six months when stored at room temperature,
wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.
Regarding instant claims 1 and 28, Zhong-1 teaches a microbial agent comprising a bacterial cellulose and a microorganism (Abstract). Zhong-1 teaches the bacterial cellulose of the agent protects the activity of the microorganism (Abstract). Zhong-1 teaches the microorganism of the agent includes probiotics and lactobacillus (translation, p. 7, paragraph [0019]). Zhong-1 teaches that the bacterial cellulose is made into granules and sterilized before combining with the microorganism in a culture medium and culturing the microorganism in the presence of the bacterial cellulose (translation at paragraph [0015]). Zhong-1 teaches the agent comprising a bacterial cellulose and an applied microorganism is subjected to a drying process (translation at paragraph [0021]).
Differences between Zhong-1 and instant claims 1 and 28 are addressed below.
While Zhong-1 teaches the microbial agent comprises a bacterial cellulose (Abstract), Zhong-1 does not teach the bacterial cellulose is a nanocellulose multiphase biomaterial as recited in claim 1.
Hessler generally teaches a multiphase biomaterial that is based on bacterial nanocellulose (paragraph [0001]), which is suitable for a broad range of applications due to highly versatile determinable structures and material properties (paragraph [0002]) without requiring disadvantageous additives or composite formations produced in the synthesis with them (paragraph [0003]). Hessler teaches a method for synthesizing the multiphase bacterial nanocellulose (beginning at paragraph [0048]).
In view of the combined teachings of Zhong-1 and Hessler, it would have been obvious to one of ordinary skill in the art before the effective filing date to use the multiphase bacterial nanocellulose of Hessler as the bacterial cellulose of the microbial agent of Zhong-1. One would have been motivated and would have expected success to do this because Zhong-1 taught the agent comprises a bacterial cellulose and Hessler taught a bacterial cellulose that is suitable for a broad range of applications with advantageous characteristics including highly versatile determinable structures and material properties.
While Zhong-1 teaches the microorganism includes probiotics and lactobacillus (translation, p. 7, paragraph [0019]) and teaches applying the microorganism to the bacterial cellulose by culturing the microorganism in the presence of the bacterial cellulose (p. 6, paragraph [0015]), Zhong-1 does not teach the microorganism is Lactococcus lactis, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus fermentum, Bacillus subtilis, or Bacillus megaterium and applying the microorganism by spraying as recited in claim 1.
Zhong-2 teaches methods for applying yeast to bacterial cellulose, including spraying a culture liquid of the yeast onto the bacterial cellulose (translation at p. 3, bottom; p. 4, Embodiments two, four, and six).
Spigelman teaches applying probiotic microorganisms to a surface by spraying the surface with the probiotic microorganism (paragraph [0008]). Spigelman teaches exemplary probiotic microorganisms including Lactococcus lactis, Lactobacillus rhamnosus, Lactobacillus plantarum, and Lactobacillus fermentum (paragraph [0017] and Appendix 1 beginning at p. 5).
In view of the combined teachings of Zhong-1, Zhong-2, and Spigelman, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of Zhong-1 to apply a probiotic such as Lc. lactis subsp. lactis or Lactobacillus plantarum by spraying a liquid of the probiotic onto a bacterial cellulose. One would have been motivated to do this because Zhong-1 taught applying a probiotic to a bacterial cellulose and Zhong-2 taught spraying as a method for applying a microorganism to a bacterial cellulose. One would have expected success because Zhong-2 taught spraying as a method for applying a microorganism to a bacterial cellulose and Spigelman taught applying probiotic microorganisms including Lactococcus lactis, Lactobacillus rhamnosus, Lactobacillus plantarum, and Lactobacillus fermentum to a surface by spraying.
While Zhong-1 teaches the bacterial cellulose is a freeze-drying protective agent (Abstract), and Zhong teaches the microbial agent is subjected to a freeze-drying process (translation at paragraph [0021]), Zhong-1 does not teach applying a moisture binder for freeze drying as recited in claim 1.
Fischer teaches lyophilization (i.e., freeze-drying) as an established method for bacterial nanocellulose (paragraph [0012]). Fischer teaches that while lyophilization is the method with best results for preserving the structure of bacterial nanocellulose (paragraph [0013]), methods for drying bacterial cellulose alter the structure and reduce the reswellability after drying (paragraphs [0003] to [0025]). Fisher teaches using a moisture binder for drying cellulose without disruptive stress on the cellulose and without loss of stability and efficacy of any additive substances allowing reswelling almost completely to the original structure and consistency (paragraph [0026]). The moisture binder of Fischer is an osmotically and/or hygroscopically effective solution, characterized in that the moisture-binding solution has a concentration of osmotically active and/or hygroscopic substances of 0.01% up to the saturation limit, preferably of 5-20% (claim 4 of Fischer).
In view of the combined teachings of Zhong-1 and Fischer, it would have been obvious to one of ordinary skill in the art to modify Zhong-1 to use the moisture binder of Fischer for freeze drying. One would have been motivated to and would have expected success to do so because Zhong-1 taught freeze drying the microbial agent, while Fischer taught methods for drying bacterial cellulose alter the structure and reduce the reswellability after drying and taught using a moisture binder for drying cellulose, which allows the cellulose to reswell as required almost completely to the original structure and consistency without disruptive stress on the cellulose and without loss of stability and efficacy of any additive substances.
While Zhong-1 teaches selecting appropriate process parameters for freeze-drying according to needs, and teaches a freeze-drying time of up to 15 hours (translation at paragraph [0021]), Zhong-1 does not teach freeze drying for 1-6 days or 3-5 days to a residual water content of from 3% to 14% as recited in claims 1 and 28.
Wang teaches water content is an important parameter for the stability of dried cultures and in general, microorganisms survive better at low-water activity (p. 211, column 2). Wang teaches the optimum residual moisture content varies with the composition of the fluid in which the microorganisms are dried, with the storage atmosphere and with the species of organisms (p. 211, column 2, bottom). Wang teaches freeze-drying a probiotic Lactobacillus strain at –50oC and 1.5 mmHg vacuum for about 50 hours (p. 210, column 2), which resulted in a moisture content of 2.9% to 3.5% (p. 212, column 1).
According to MPEP 2144.05.II.A, "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." As taught by Wang, freeze-drying time is a parameter of the freeze-drying process to achieve a desired low residual moisture content. In view of the combined teachings of Zhong-1 and Wang, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify Zhong-1 to select an optimal and/or workable range of freeze drying time of 1-6 days or 3-5 days along with other freeze-drying parameters in order to achieve a desired residual moisture content of from 3% to 14%.
While Zhong-1 teaches the microbial agent maintains a high number of live bacteria after long term storage (paragraph [0009]) and after long-term storage, the microorganisms still have strong activity (paragraph [0024]), Zhong-1 does not teach the microorganism component of the microbial agent retains viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard as recited in claim 1.
Wang teaches that following a freeze-drying process for fermented soymilk comprising lactic acid bacteria, the product was stored in a laminated pouch comprising nylon/aluminum/retort coated polypropylene, which was vacuum sealed before storage (p. 210, column 2, bottom). Wang teaches 38% survival of S. thermophilus and 61% survival of B. longum in the freeze-dried product after storage in the laminated pouch for 4 months at room temperature (p. 214, Table 5).
Given the teachings of Wang, one of ordinary skill in the art would have reasonably expected that the microbial agent made according to the combination of Zhong-1, Hessler, Othman, Spigelman, Fischer, and Wang would have retained viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.
Moreover, according to MPEP 2112.01.I, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Since the combination of cited prior art teaches and/or suggests all active steps of claim 1 that must be performed to make the microorganism loaded multiphase biomaterial comprising nanocellulose, it is presumed that the microbial agent made according to the combination of Zhong-1, Hessler, Othman, Spigelman, Fischer, and Wang would have retained viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.
In the interest of clarity, it is noted that the recitation of “wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard” is interpreted as setting forth the method for measuring viability but does not require active steps of measuring by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard in order to practice the claimed method.
Regarding instant claim 3, Spigelman teaches that generally, probiotic microorganisms may be viable or may be in the form of a spore (paragraph [0027]).
Regarding instant claim 4, modifying Zhong-1 to apply a probiotic such as Lc. lactis subsp. lactis or Lactobacillus plantarum by spraying a liquid of the probiotic onto a bacterial cellulose would use a “wet” microorganism.
Regarding instant claim 5, by modifying Zhong-1 to apply a probiotic such as Lc. lactis subsp. lactis or Lactobacillus plantarum to spray a liquid of the probiotic onto a bacterial cellulose would result in a “wet” bacterial cellulose.
Regarding instant claim 6, the bacterial cellulose of Hessler is derived from bacteria.
Regarding instant claim 7, Hessler teaches the bacterial cellulose comprises layered phases (paragraphs [0022] and [0023]).
Regarding instant claims 8 and 22, Hessler teaches the thickness of the individual phases and the resulting properties can be controlled by shifting the inoculation ratio to produce the BNC (paragraph [0046]), and Zhong-1 teaches that the bacterial cellulose particles preferably have a side length of 3 to 8 mm (translation at p. 7, paragraph [0018]).
Regarding instant claim 9, Hessler teaches a plurality of bacterial cellular networks that form a homogenous phase system (paragraph [0023]).
Regarding instant claim 10, Hessler summarizes methods for modifying homogeneous or multi-phase biomaterials based on BNC (beginning at paragraph [0004]) teaching that carboxymethyl cellulose (CMC) and methyl cellulose (MC) affect the pore size of the BNC network (paragraph [0007]).
Regarding instant claim 13, Spigelman teaches the probiotic bacteria include Lactobacillus lactis (subsp. Lactis (paragraph [0017]).
Regarding instant claim 14, Spigelman teaches that viability of probiotics may be facilitated by incorporation of nutrients such as amino acids (paragraph [0027]).
Regarding instant claim 24, Fischer teaches glucose or magnesium chloride as the moisture binder (paragraph [0054] and Figure 3).
Regarding instant claim 26, Wang teaches that following a freeze-drying process for fermented soymilk comprising lactic acid bacteria, the product was stored in a laminated pouch comprising nylon/aluminum/retort coated polypropylene, which was vacuum sealed before storage (p. 210, column 2, bottom). Wang teaches the moisture content of the freeze-dried product had an initial moisture content of 3.09% and after storage in the laminated pouch at 4oC or 25oC for four months had a moisture content of 3.09% and 3.10%, respectively (p. 214, Table 5). Wang teaches storage in the laminated pouch increases survivability relative to storage in a glass or PET bottle (p. 215, Figure 2; p. 216, column 1). The vacuum-sealed laminated pouch of Wang is considered to be encompassed by “a humidity-impermeable aluminum composite foil.”
Therefore, the invention of claims 1, 3-10, 13, 14, 22, 24, 26, and 28 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 19, 23, 25, 27, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong-1 in view of Hessler, Othman et al. (AMB Expr. 7:215, 2017, 14 pages; cited on Form PTO-892 filed September 26, 2025; hereafter “Othman”), Spigelman, Fischer, and Wang.
This rejection has been modified from its previous version in order to address applicant’s amendments to the claims.
As amended, claim 19 is drawn to a method for making a microorganism loaded multiphase biomaterial comprising nanocellulose, the method comprising:
synthesizing a nanocellulose (BNC) multiphase biomaterial;
resuspending the microorganism in a buffer or a culture medium, and
loading the microorganism into and/or onto the nanocellulose multiphase biomaterial by (1) mixing the nanocellulose multiphase biomaterial with the microorganisms at 300 rpm or more at a temperature of 37° C or less, (2) injecting the microorganisms into the nanocellulose multiphase biomaterial and incubating at a temperature of 37° C or less, or (3) incubating the nanocellulose multiphase biomaterial in the buffer or culture medium with resuspended microorganisms at a temperature of 37° C or less for 60 min or less,
wherein the microorganism is at least one selected from the group consisting of Lactococcus lactis, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus fermentum, Bacillus subtilis, and Bacillus megaterium;
incubating the loaded nanocellulose multiphase biomaterial with a moisture binder for drying, wherein the moisture binder is an osmotically and/or hygroscopically effective moisture-binding solution having a concentration of osmotically active and/or hygroscopic substances of 5 to 20%; and
freeze drying the nanocellulose multiphase biomaterial treated with moisture binder for 1-6 days to a residual water content of from 3% to 14%;
to thereby provide the microorganism loaded multiphase biomaterial comprising nanocellulose;
wherein the microorganism component of the microorganism loaded multiphase biomaterial comprising nanocellulose retains viability for at least six months when stored at room temperature,
wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.
Regarding instant claims 19 and 29, Zhong-1 teaches a microbial agent comprising a bacterial cellulose and a microorganism (Abstract). Zhong-1 teaches the bacterial cellulose of the agent protects the activity of the microorganism (Abstract). Zhong-1 teaches the microorganism of the agent includes probiotics and lactobacillus (translation, p. 7, paragraph [0019]). Zhong-1 teaches that the bacterial cellulose is made into granules and sterilized before combining with the microorganism in a culture medium and culturing the microorganism in the presence of the bacterial cellulose (translation at paragraph [0015]). Zhong-1 teaches the agent comprising a bacterial cellulose and an applied microorganism is subjected to a drying process (translation at paragraph [0021]).
Differences between Zhong-1 and claims 19 and 29 are addressed below.
While Zhong-1 teaches the microbial agent comprises a bacterial cellulose (Abstract), Zhong-1 does not teach the bacterial cellulose is a nanocellulose multiphase biomaterial as recited in claim 19.
Hessler generally teaches a multiphase biomaterial that is based on bacterial nanocellulose (paragraph [0001]), which is suitable for a broad range of applications due to highly versatile determinable structures and material properties (paragraph [0002]) without requiring disadvantageous additives or composite formations produced in the synthesis with them (paragraph [0003]). Hessler teaches a method for synthesizing the multiphase bacterial nanocellulose (beginning at paragraph [0048]).
In view of the combined teachings of Zhong-1 and Hessler, it would have been obvious to one of ordinary skill in the art before the effective filing date to use the multiphase bacterial nanocellulose of Hessler as the bacterial cellulose of the microbial agent of Zhong-1. One would have been motivated to and would have had a reasonable expectation of success to do this because Zhong-1 taught the agent comprises a bacterial cellulose and Hessler taught a bacterial cellulose that is suitable for a broad range of applications with advantageous characteristics including highly versatile determinable structures and material properties.
While Zhong-1 teaches the microorganism includes probiotics and lactobacillus (translation at paragraph [0019]) and teaches applying the microorganism to the bacterial cellulose by culturing a microorganism in the presence of the bacterial cellulose at 37° C (translation at paragraphs [0015], [0031], [0032], [0040], [0041], [0050], and [0051]), Zhong-1 does not teach applying the microorganism by mixing the nanocellulose multiphase biomaterial with the microorganisms at 300 rpm, and does not teach the microorganism is Lactococcus lactis, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus fermentum, Bacillus subtilis, or Bacillus megaterium as recited in claim 19.
Othman teaches an evaluation of agitation speed on growth of a probiotic lactic acid bacterium, noting that increasing agitation speed from 200 to 300 rpm improved viable cell concentration, viable cell yield, viable cell productivity, lactic acid production, lactic acid yield and lactic acid productivity (paragraph bridging pp. 6-7). Othman teaches these results are in agreement with a previous observation of improved growth of Lactobacillus plantarum in the presence of oxygen compared to anaerobic condition (p. 11, column 2, middle).
Spigelman teaches exemplary probiotic microorganisms including Lactococcus lactis, Lactobacillus rhamnosus, Lactobacillus plantarum, and Lactobacillus fermentum (paragraph [0017] and Appendix 1 beginning at p. 5).
In view of the combined teachings of Zhong-1, Othman, and Spigelman, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of Zhong-1 to use an agitation speed of 300 rpm to apply a probiotic such as Lactococcus lactis, Lactobacillus rhamnosus, Lactobacillus plantarum, or Lactobacillus fermentum to a nanocellulose multiphase biomaterial. One would have been motivated to and would have expected success to do this because, while Zhong-1 teaches applying a microorganism to bacterial cellulose by culturing a microorganism in the presence of the bacterial cellulose at 37° C, Zhong-1 does not teach an agitation speed for the culturing and Othman teaches an agitation speed of 300 rpm for improved viable cell concentration, viable cell yield, viable cell productivity, lactic acid production, lactic acid yield and lactic acid productivity, and Spigelman teaches exemplary probiotic microorganisms including Lactococcus lactis, Lactobacillus rhamnosus, and Lactobacillus plantarum, and Lactobacillus fermentum.
While Zhong-1 teaches the bacterial cellulose is a freeze-drying protective agent (Abstract), and Zhong teaches the microbial agent is subjected to a freeze-drying process (translation at paragraph [0021]), Zhong-1 does not teach applying a moisture binder for freeze drying as recited in claim 19.
Fischer teaches lyophilization (i.e., freeze-drying) as an established method for bacterial nanocellulose (paragraph [0012]). Fischer teaches that while lyophilization is the method with best results for preserving the structure of bacterial nanocellulose (paragraph [0013]), methods for drying bacterial cellulose alter the structure and reduce the reswellability after drying (paragraphs [0003] to [0025]). Fisher teaches uses a moisture binder for drying cellulose without disruptive stress on the cellulose and without loss of stability and efficacy of any additive substances allowing reswelling almost completely to the original structure and consistency (paragraph [0026]). The moisture binder of Fischer is an osmotically and/or hygroscopically effective solution, characterized in that the moisture-binding solution has a concentration of osmotically active and/or hygroscopic substances of 0.01% up to the saturation limit, preferably of 5-20% (claim 4 of Fischer).
In view of the combined teachings of Zhong-1 and Fischer, it would have been obvious to one of ordinary skill in the art to further modify Zhong-1 to use the moisture binder of Fischer for freeze drying. One would have been motivated to and would have had a reasonable expectation of success to do so because Zhong-1 taught freeze drying the microbial agent, while Fischer taught methods for drying bacterial cellulose alter the structure and reduce the reswellability after drying and taught using a moisture binder for drying cellulose, which allows the cellulose to reswell as required almost completely to the original structure and consistency without disruptive stress on the cellulose and without loss of stability and efficacy of any additive substances.
While Zhong-1 teaches selecting appropriate process parameters for freeze-drying according to needs, and teaches a freeze-drying time of up to 15 hours (translation at paragraph [0021]), Zhong-1 does not teach freeze drying for 1-6 days or 3-5 days to a residual water content of from 3% to 14% as recited in claims 19 and 29.
Wang teaches water content is an important parameter for the stability of dried cultures and in general, microorganisms survive better at low-water activity (p. 211, column 2). Wang teaches freeze-drying a probiotic Lactobacillus strain at –50oC and 1.5 mmHg vacuum for about 50 hours (p. 210, column 2), which resulted in a moisture content of 2.9% to 3.5% (p. 212, column 1).
According to MPEP 2144.05.II.A, "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." As taught by Wang, freeze-drying time is a parameter of the freeze-drying process to achieve a desired low residual moisture content. In view of the combined teachings of Zhong-1 and Wang, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify Zhong-1 to select an optimal and/or workable range of freeze drying time of 1-6 days or 3-5 days along with other freeze-drying parameters in order to achieve a desired residual moisture content of from 3% to 14%.
While Zhong-1 teaches the microbial agent maintains a high number of live bacteria after long term storage (paragraph [0009]) and after long-term storage, the microorganisms still have strong activity (paragraph [0024]), Zhong-1 does not teach the microorganism component of the microbial agent retains viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard as recited in claim 19.
Wang teaches that following a freeze-drying process for fermented soymilk comprising lactic acid bacteria, the product was stored in a laminated pouch comprising nylon/aluminum/retort coated polypropylene, which was vacuum sealed before storage (p. 210, column 2, bottom). Wang teaches 38% survival of S. thermophilus and 61% survival of B. longum in the freeze-dried product after storage in the laminated pouch for 4 months at room temperature (p. 214, Table 5).
Given the teachings of Wang, one of ordinary skill in the art would have reasonably expected that the microbial agent made according to the combination of Zhong-1, Hessler, Othman, Spigelman, Fischer, and Wang would retain viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.
Moreover, according to MPEP 2112.01.I, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Since the combination of cited prior art teaches and/or suggests all active steps of claim 1 that must be performed to make the microorganism loaded multiphase biomaterial comprising nanocellulose, it is presumed that the microbial agent made according to the combination of Zhong-1, Hessler, Othman, Spigelman, Fischer, and Wang would retain viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.
In the interest of clarity, it is noted that the recitation of “wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard” is interpreted as setting forth the method for measuring viability but does not require active steps of measuring by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard in order to practice the claimed method.
Regarding instant claim 23, Hessler teaches the thickness of the individual phases and the resulting properties can be controlled by shifting the inoculation ratio to produce the BNC (paragraph [0046]), and Zhong-1 teaches that the bacterial cellulose particles preferably have a side length of 3 to 8 mm (translation at p. 7, paragraph [0018]).
Regarding instant claim 25, Fischer teaches glucose or magnesium chloride as the moisture binder (paragraph [0054] and Figure 3).
Regarding instant claim 27, Wang teaches that following a freeze-drying process for fermented soymilk comprising lactic acid bacteria, the product was stored in a laminated pouch comprising nylon/aluminum/retort coated polypropylene, which was vacuum sealed before storage (p. 210, column 2, bottom). Wang teaches the moisture content of the freeze-dried product had an initial moisture content of 3.09% and after storage in the laminated pouch at 4oC or 25oC for four months had a moisture content of 3.09% and 3.10%, respectively (p. 214, Table 5). Wang teaches storage in the laminated pouch increases survivability relative to storage in a glass or PET bottle (p. 215, Figure 2; p. 216, column 1). The vacuum-sealed laminated pouch of Wang is considered to be encompassed by “a humidity-impermeable aluminum composite foil.”
Therefore, the invention of claims 19, 23, 25, 27, and 29 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 19, 23, 25, 27, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Zhong-1 in view of Hessler, Zhong-2, Spigelman, Fischer, and Wang.
This rejection has been modified from its previous version in order to address applicant’s amendments to the claims.
Regarding instant claims 19 and 29, Zhong-1 teaches a microbial agent comprising a bacterial cellulose and a microorganism (Abstract). Zhong-1 teaches the bacterial cellulose of the agent protects the activity of the microorganism (Abstract). Zhong-1 teaches the microorganism of the agent includes probiotics and lactobacillus (translation, p. 7, paragraph [0019]). Zhong-1 teaches that the bacterial cellulose is made into granules and sterilized before combining with the microorganism in a culture medium and culturing the microorganism in the presence of the bacterial cellulose (translation at paragraph [0015]). Zhong-1 teaches the agent comprising a bacterial cellulose and an applied microorganism is subjected to a drying process (translation at paragraph [0021]).
Differences between Zhong-1 and claims 19 and 29 are addressed below.
While Zhong-1 teaches the microbial agent comprises a bacterial cellulose (Abstract), Zhong-1 does not teach the bacterial cellulose is a nanocellulose multiphase biomaterial as recited in claim 19.
Hessler generally teaches a multiphase biomaterial that is based on bacterial nanocellulose (paragraph [0001]), which is suitable for a broad range of applications due to highly versatile determinable structures and material properties (paragraph [0002]) without requiring disadvantageous additives or composite formations produced in the synthesis with them (paragraph [0003]). Hessler teaches a method for synthesizing the multiphase bacterial nanocellulose (beginning at paragraph [0048]).
In view of the combined teachings of Zhong-1 and Hessler, it would have been obvious to one of ordinary skill in the art before the effective filing date to use the multiphase bacterial nanocellulose of Hessler as the bacterial cellulose of the microbial agent of Zhong-1. One would have been motivated to and would have had a reasonable expectation of success to do this because Zhong-1 taught the agent comprises a bacterial cellulose and Hessler taught a bacterial cellulose that is suitable for a broad range of applications with advantageous characteristics including highly versatile determinable structures and material properties.
While Zhong-1 teaches the microorganism includes probiotics and lactobacillus (translation at paragraph [0019]) and teaches applying the microorganism to the bacterial cellulose by culturing a microorganism in the presence of the bacterial cellulose at 37° C for a time of 5, 10, or 12 hours (translation at paragraphs [0015], [0031], [0032], [0040], [0041], [0050], and [0051]), Zhong-1 does not teach applying the microorganism by incubating the nanocellulose multiphase biomaterial in culture medium with resuspended microorganisms for less for 60 min or less, and does not teach the microorganism is Lactococcus lactis, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus fermentum, Bacillus subtilis, or Bacillus megaterium as recited in claim 19.
Zhong-2 teaches methods for applying yeast to bacterial cellulose, including culturing a microorganism (yeast) with bacterial cellulose at room temperature for 2 or 4 hours (translation at p. 4, Embodiments one and five).
Spigelman teaches exemplary probiotic microorganisms including Lactococcus lactis, Lactobacillus rhamnosus, Lactobacillus plantarum, and Lactobacillus fermentum (paragraph [0017] and Appendix 1 beginning at p. 5).
In view of the combined teachings of Zhong-1, Zhong-2, and Spigelman, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the method of Zhong-1 to apply a probiotic such as Lactococcus lactis, Lactobacillus rhamnosus, Lactobacillus plantarum, or Lactobacillus fermentum by incubating the nanocellulose multiphase biomaterial in culture medium with resuspended microorganisms at a temperature of 37° C or less for 60 min or less. According to MPEP 2144.05.II.A, "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." Given that Zhong-1 and Zhong-2 each teaches various temperatures and times for applying a microorganism to a bacterial cellulose and Spigelman teaches exemplary probiotic microorganisms, it would have been obvious to one of ordinary skill in the art at the time of the invention to select parameters for incubating a multiphase bacterial nanocellulose with a probiotic such as Lactococcus lactis, Lactobacillus rhamnosus, Lactobacillus plantarum, or Lactobacillus fermentum to achieve an optimal and/or workable range of temperatures and times.
While Zhong-1 teaches the bacterial cellulose is a freeze-drying protective agent (Abstract), and Zhong teaches the microbial agent is subjected to a freeze-drying process (translation at paragraph [0021]), Zhong-1 does not teach applying a moisture binder for freeze drying as recited in claim 19.
Fischer teaches lyophilization (i.e., freeze-drying) as an established method for bacterial nanocellulose (paragraph [0012]). Fischer teaches that while lyophilization is the method with best results for preserving the structure of bacterial nanocellulose (paragraph [0013]), methods for drying bacterial cellulose alter the structure and reduce the reswellability after drying (paragraphs [0003] to [0025]). Fisher teaches uses a moisture binder for drying cellulose without disruptive stress on the cellulose and without loss of stability and efficacy of any additive substances allowing reswelling almost completely to the original structure and consistency (paragraph [0026]). The moisture binder of Fischer is an osmotically and/or hygroscopically effective solution, characterized in that the moisture-binding solution has a concentration of osmotically active and/or hygroscopic substances of 0.01% up to the saturation limit, preferably of 5-20% (claim 4 of Fischer).
In view of the combined teachings of Zhong-1 and Fischer, it would have been obvious to one of ordinary skill in the art to further modify Zhong-1 to use the moisture binder of Fischer for freeze drying. One would have been motivated to and would have had a reasonable expectation of success to do so because Zhong-1 taught freeze drying the microbial agent, while Fischer taught methods for drying bacterial cellulose alter the structure and reduce the reswellability after drying and taught using a moisture binder for drying cellulose, which allows the cellulose to reswell as required almost completely to the original structure and consistency without disruptive stress on the cellulose and without loss of stability and efficacy of any additive substances.
While Zhong-1 teaches selecting appropriate process parameters for freeze-drying according to needs, and teaches a freeze-drying time of up to 15 hours (translation at paragraph [0021]), Zhong-1 does not teach freeze drying for 1-6 days or 3-5 days to a residual water content of from 3% to 14% as recited in claims 19 and 29.
Wang teaches water content is an important parameter for the stability of dried cultures and in general, microorganisms survive better at low-water activity (p. 211, column 2). Wang teaches freeze-drying a probiotic Lactobacillus strain at –50oC and 1.5 mmHg vacuum for about 50 hours (p. 210, column 2), which resulted in a moisture content of 2.9% to 3.5% (p. 212, column 1).
In view of the combined teachings of Zhong-1 and Wang, it would have been obvious to one of ordinary skill in the art to further modify Zhong-1 to select freeze drying parameters of 1-6 days to a residual water content of from 3% to 14%. According to MPEP 2144.05.II.A, "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." Given that Zhong-1 teaches selecting appropriate process parameters for freeze-drying according to needs, Wang teaches water content is an important parameter for the stability of dried cultures and in general, microorganisms survive better at low-water activity, and teaches freeze-drying a probiotic Lactobacillus strain for about 50 hours, which resulted in a moisture content of 2.9% to 3.5%, it would have been obvious to one of ordinary skill in the art at the time of the invention to select freeze drying parameters that achieve an optimal and/or workable range of freeze drying time and residual water content.
While Zhong-1 teaches the microbial agent maintains a high number of live bacteria after long term storage (paragraph [0009]) and after long-term storage, the microorganisms still have strong activity (paragraph [0024]), Zhong-1 does not teach the microorganism component of the microbial agent retains viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard as recited in claim 19.
Wang teaches that following a freeze-drying process for fermented soymilk comprising lactic acid bacteria, the product was stored in a laminated pouch comprising nylon/aluminum/retort coated polypropylene, which was vacuum sealed before storage (p. 210, column 2, bottom). Wang teaches 38% survival of S. thermophilus and 61% survival of B. longum in the freeze-dried product after storage in the laminated pouch for 4 months at room temperature (p. 214, Table 5).
Given the teachings of Wang, one of ordinary skill in the art would have reasonably expected that the microbial agent made according to the combination of Zhong-1, Hessler, Othman, Spigelman, Fischer, and Wang would have retained viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.
Moreover, according to MPEP 2112.01.I, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Since the combination of cited prior art teaches and/or suggests all active steps of claim 1 that must be performed to make the microorganism loaded multiphase biomaterial comprising nanocellulose, it is presumed that the microbial agent made according to the combination of Zhong-1, Hessler, Othman, Spigelman, Fischer, and Wang would have retained viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.
In the interest of clarity, it is noted that the recitation of “wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard” is interpreted as setting forth the method for measuring viability but does not require active steps of measuring by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard in order to practice the claimed method.
Regarding instant claim 23, Hessler teaches the thickness of the individual phases and the resulting properties can be controlled by shifting the inoculation ratio to produce the BNC (paragraph [0046]), and Zhong-1 teaches that the bacterial cellulose particles preferably have a side length of 3 to 8 mm (translation at p. 7, paragraph [0018]).
Regarding instant claim 25, Fischer teaches glucose or magnesium chloride as the moisture binder (paragraph [0054] and Figure 3).
Regarding instant claim 27, Wang teaches that following a freeze-drying process for fermented soymilk comprising lactic acid bacteria, the product was stored in a laminated pouch comprising nylon/aluminum/retort coated polypropylene, which was vacuum sealed before storage (p. 210, column 2, bottom). Wang teaches the moisture content of the freeze-dried product had an initial moisture content of 3.09% and after storage in the laminated pouch at 4oC or 25oC for four months had a moisture content of 3.09% and 3.10%, respectively (p. 214, Table 5). Wang teaches storage in the laminated pouch increases survivability relative to storage in a glass or PET bottle (p. 215, Figure 2; p. 216, column 1). The vacuum-sealed laminated pouch of Wang is considered to be encompassed by “a humidity-impermeable aluminum composite foil.”
Therefore, the invention of claims 19, 23, 25, 27, and 29 would have been obvious to one of ordinary skill in the art before the effective filing date.
RESPONSE TO REMARKS: Applicant argues the rejections under 35 U.S.C. 103 are obviated by amendments to claims 1 and 19 to recite “wherein the microorganism component of the microorganism loaded multiphase biomaterial comprising nanocellulose retains viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.”
Applicant’s arguments are not found persuasive. The noted limitation has been fully addressed in the rejections set forth above. In summary, Wang teaches that following a freeze-drying process for fermented soymilk comprising lactic acid bacteria, the product was stored in a laminated pouch comprising nylon/aluminum/retort coated polypropylene, which was vacuum sealed before storage (p. 210, column 2, bottom). Wang teaches 38% survival of S. thermophilus and 61% survival of B. longum in the freeze-dried product after storage in the laminated pouch for 4 months at room temperature (p. 214, Table 5).
Given the teachings of Wang, one of ordinary skill in the art would have reasonably expected that the microbial agent made according to the combination of Zhong-1, Hessler, Othman, Spigelman, Fischer, and Wang would have retained viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.
Moreover, according to MPEP 2112.01.I, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Since the combination of cited prior art teaches and/or suggests all active steps of claim 1 that must be performed to make the microorganism loaded multiphase biomaterial comprising nanocellulose, it is presumed that the microbial agent made according to the combination of Zhong-1, Hessler, Othman, Spigelman, Fischer, and Wang would have retained viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.
Applicant further argues that the rejections under 35 U.S.C. 103 are based on an improper hindsight analysis that fails to account for a synergistic nature of the claimed method.
Applicant’s arguments are not found persuasive. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See MPEP 2145.X.A. In this case, the rejections rely only on knowledge which was within the level of ordinary skill at the time the claimed invention was made, and do not include knowledge gleaned only from the applicant's disclosure. Thus, contrary to applicant’s position, the rejections rely only on knowledge which was within the level of ordinary skill at the time the claimed invention was made, and do not rely on an improper hindsight analysis.
For these reasons, it is the examiner’s position that the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Claim Rejections - 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 3-6, 8, 13, 14, 19, and 22-29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 11, and 12 of copending Application No. 17/625,955 (reference application) in view of Fischer and Wang. Although the claims at issue are not identical, they are not patentably distinct from each other for reasons that follow.
This provisional rejection has been modified from its previous version in order to address applicant’s amendment to the claims.
Regarding the limitations of “[a] method for making a microorganism loaded multiphase biomaterial comprising nanocellulose…to thereby provide the microorganism loaded multiphase biomaterial comprising nanocellulose” recited in instant claims 1 and 19, claim 1 of the reference application recites a method for loading one or more microorganisms or part(s) thereof on and/or in pre-synthesized bacterially synthesized nanocellulose (BNC) non-woven biomaterial,” and given that claims 2, 6, and 12 of the reference application each recites “the multiphase biomaterial” in reference to claim 1, one would have recognized that the biomaterial of claim 1 of the reference application is a multiphase biomaterial.
Regarding the limitation of “synthesizing a nanocellulose multiphase biomaterial” recited in instant claims 1 and 19, claim 1 of the reference application recites “synthesizing a BNC non-woven biomaterial.”
Regarding the limitation of “resuspending the microorganism in a buffer or a culture medium” recited in instant claims 1 and 19, claim 1 of the reference application recites “resuspending the one or more microorganisms in a buffer or a culture medium.”
Regarding the limitation of “loading the microorganism into and/or onto the nanocellulose multiphase biomaterial by spraying the microorganism onto the multiphase biomaterial” recited in instant claim 1 of this application, claim 2 of the reference application recites (in relevant part) the method of claim 1, wherein the one or more microorganisms resuspended in the buffer or culture medium are loaded into and/or onto the BNC non-woven material by d) spraying the one or more microorganisms resuspended in the buffer or culture medium at a temperature of 37°C or less for 60 min or less.
Regarding the limitation of “loading the microorganism into and/or onto the nanocellulose multiphase biomaterial by (1) mixing the nanocellulose multiphase biomaterial with the microorganisms at 300 rpm or more at a temperature of 37° C or less, (2) injecting the microorganisms into the nanocellulose multiphase biomaterial and incubating at a temperature of 37° C or less, or (3) incubating the nanocellulose multiphase biomaterial in the buffer or culture medium with resuspended microorganisms at a temperature of 37° C or less for 60 min or less” recited in instant claim 19, claim 2 of the reference application recites (in relevant part) the method of claim 1, wherein the one or more microorganisms resuspended in the buffer or culture medium are loaded into and/or onto the BNC non-woven biomaterial by a) mixing a multiphase biomaterial with the one or more microorganisms resuspended in the buffer or culture medium at 300 rpm or more, for 1 to 60 min, at a temperature of 37°C or less, or b) injecting the one or more microorganisms resuspended in the buffer or culture medium into the multiphase biomaterial and incubating at a temperature of 37°C or less for up to 72h, or, c) incubating the multiphase biomaterial in the buffer or culture medium with the one or more microorganisms resuspended at a temperature of 37°C or less for 60 min or less.
Regarding the limitation of “wherein the microorganism is at least one selected from the group consisting of Lactococcus lactis, Lactobacillus rhamnosus, Lactobacillus plantarum, Lactobacillus fermentum, Bacillus subtilis, and Bacillus megaterium” recited in instant claims 1 and 19, claim 11 of the reference application recites (in relevant part) the method of claim 1, wherein the microorganism is L. fermentum, DSM 32609 L. rhamnosus, DSM 32758 L. plantarum, L. plantarum LNS, DSM 33368 L. plantarum S3, DSM 33369 L. plantarum S11, DSM 33367 L. plantarum F8, DSM 33366 L. plantarum S4, DSM 33364 L. plantarum S28, DSM 33363 L. plantarum S27, DSM 33365 L. plantarum S18b, DSM 33362 L. plantarum S13, DSM 32767 Lactococcus lactis sups. lactis, and L. fermentum DSM 32750.
Regarding the limitation of “incubating the loaded nanocellulose multiphase biomaterial with a moisture binder for drying, wherein the moisture binder is an osmotically and/or hygroscopically effective moisture-binding solution having a concentration of osmotically active and/or hygroscopic substances of 5 to 20%” recited in instant claims 1 and 19, claim 1 of the reference application recites (in relevant part) incubating the BNC non-woven biomaterial with an osmotically and/or hygroscopically effective solution, and claim 9 of the reference application recites wherein the osmotically and/or hygroscopically effective solution contains single saccharides, salts, saccharide-containing or saccharide-like substances, polyethylene oxides, a combination of different representatives of these moisture-binding groups of substances and/or a combination of one and/or more representatives of these moisture-binding groups of substances with one or more surfactants and/or one or more preservatives.
The claims of the reference application do not specify a concentration of the moisture binding solution for drying cellulose.
Fischer teaches a moisture binder for cellulose, which is an osmotically and/or hygroscopically effective solution is used containing in particular single saccharides, salts, saccharide-containing or saccharide-like substances, polyethylene oxides, a combination of different representatives of these moisture-binding groups of substances and/or a combination of one and/or more representatives of these moisture-binding groups of substances with one or more surfactants and/or one or more preservatives, characterized in that the moisture-binding solution has a concentration of osmotically active and/or hygroscopic substances of 0.01% up to the saturation limit, preferably of 5-20% (claim 4 of Fischer).
In view of the teachings of Fischer, it would have been obvious to one of ordinary skill in the art for the moisture binding solution of claim 9 of the reference application to have a concentration of osmotically active and/or hygroscopic substances of 0.01% up to the saturation limit, preferably of 5-20%. One would have been motivated to and would have had a reasonable expectation of success to do so because of the teachings of Fischer regarding a moisture binding solution for cellulose.
Regarding the limitation of “freeze drying the nanocellulose multiphase biomaterial treated with moisture binder for 1-6 days to a residual water content of 14% or less” recited in instant claims 1 and 19, claim 1 of the reference application recites freeze-drying the loaded BNC non-woven biomaterial for at least 24 hours to a residual water content of 20% or less.
Regarding the limitation “wherein the microorganism component of the microbial agent retains viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard as recited in instant claims 1 and 19, the claims of the reference application do not recite this limitation.
Wang teaches that following a freeze-drying process for fermented soymilk comprising lactic acid bacteria, the product was stored in a laminated pouch comprising nylon/aluminum/retort coated polypropylene, which was vacuum sealed before storage (p. 210, column 2, bottom). Wang teaches 38% survival of S. thermophilus and 61% survival of B. longum in the freeze-dried product after storage in the laminated pouch for 4 months at room temperature (p. 214, Table 5).
Given the teachings of Wang, one of ordinary skill in the art would have reasonably expected that the freeze dried, loaded BNC made according to the claims of the reference application would retain viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.
Moreover, according to MPEP 2112.01.I, when the structure recited in the reference is substantially identical to that of the claims, claimed properties or functions are presumed to be inherent. Since the method of the claims of the reference application as modified according to Fischer teaches and/or suggests all active steps of claims 1 and 19 that must be performed to make the microorganism loaded multiphase biomaterial comprising nanocellulose, it is presumed that the biomaterial made according to the method of the claims of the reference application as modified according to Fischer would retain viability for at least six months when stored at room temperature, wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard.
In the interest of clarity, it is noted that the recitation of “wherein the viability is measured by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard” is interpreted as setting forth the method for measuring viability but does not require active steps of measuring by an assay comprising culturing in MRS broth medium or isotonic saline NaCl 0.9% and measuring optical density at OD600 relative to the McFarland standard in order to practice the claimed method.
Regarding claim 3 of this application, claim 4 of the reference application recites (in relevant part) the method of claim 1, wherein the microorganisms are loaded as vegetative cells or in a dormant form.
Regarding claim 4 of this application, claim 5 of the reference application recites the method of claim 1, wherein the microorganisms are wet or dry and/or pre-cultured or not pre-cultured.
Regarding claim 5 of this application, claim 6 of the reference application recites the method of claim 1, wherein the multiphase biomaterial is wet or dried or partially dried or re-swelled in buffer.
Regarding claim 6 of this application, claim 7 of the reference application recites the method of claim 1, wherein the nanocellulose is derived from a plant, algae, or a microorganism.
Regarding claim 8 of this application, claim 8 of the reference application recites the method of claim 1, wherein the BNC non-woven biomaterial has an average thickness of at least 0.5 mm.
Regarding claim 13 of this application, claim 11 of the reference application recites (in relevant part) the method of claim 1, wherein the probiotic microorganism is L. fermentum, DSM 32609 L. rhamnosus, DSM 32758 L. plantarum, L. plantarum LNS, DSM 33368 L. plantarum S3, DSM 33369 L. plantarum S11, DSM 33367 L. plantarum F8, DSM 33366 L. plantarum S4, DSM 33364 L. plantarum S28, DSM 33363 L. plantarum S27, DSM 33365 L. plantarum S18b, DSM 33362 L. plantarum S13, DSM 32767 Lactococcus lactis sups. lactis, and L. fermentum DSM 32750.
Regarding claim 14 of this application, claim 12 of the reference application recites the method of claim 1, further comprising, before or after or in parallel to loading of the multiphase biomaterials with the microorganisms: loading the multiphase biomaterials with further ingredients and/or nutrients comprising an amino acid, fatty acid salt, anthocyanin, monosaccharide, and/or extract.
Regarding claims 22 and 23 of this application, claim 8 of the reference application recites the method of claim 1, wherein the BNC non-woven biomaterial has an average thickness of at least 0.5 mm. The range of “2-3 mm” in instant claims 22 and 23 falls within the range of “at least 0.5 mm” in claim 8 of the reference application and according to MPEP 2144.05, in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art a prima facie case of obviousness exists.
Regarding claims 24 and 25 of this application, Fischer teaches glucose or magnesium chloride as the moisture binder (paragraph [0054] and Figure 3).
Regarding claims 26 and 27 of this application, claim 3 of the reference application recites positioning the loaded BNC non-woven biomaterial between two foils for freeze-drying; and/or packaging the freeze-dried loaded BNC non-woven biomaterial in a compound foil and sealing the compound foil. Claim 3 of the reference application does not recite “a humidity-impermeable aluminum composite foil.”
Wang teaches moisture is detrimental to dry culture (p. 214, column 2, bottom). Wang teaches that following a freeze-drying process for fermented soymilk comprising lactic acid bacteria, the product was stored in a laminated pouch comprising nylon/aluminum/retort coated polypropylene, which was vacuum sealed before storage (p. 210, column 2, bottom). Wang teaches the moisture content of the freeze-dried product had an initial moisture content of 3.09% and after storage in the laminated pouch at 4oC or 25oC for four months had a moisture content of 3.09% and 3.10%, respectively (p. 214, Table 5). Wang teaches storage in the laminated pouch increases survivability relative to storage in a glass or PET bottle (p. 215, Figure 2; p. 216, column 1).
In view of Wang, it would have been obvious to one of ordinary skill in the art for the compound foil of claim 3 of the reference application to be a humidity-impermeable aluminum compound foil. One would have been motivated and expected success because claim 3 of the reference application recites packaging the freeze-dried loaded BNC non-woven biomaterial in a compound foil, Wang teaches moisture is detrimental to dry culture, and teaches a laminated pouch comprising nylon/aluminum/retort coated polypropylene for storage of a freeze-dried culture, which is considered to be a “a humidity-impermeable aluminum composite foil.”
Regarding claims 28 and 29 of this application, claim 1 of the reference application recites freeze-drying the loaded BNC non-woven biomaterial for at least 24 hours to a residual water content of 20% or less. The range of “3-5 days” in instant claims 28 and 29 falls within the range of “at least 24 hours” in claim 1 of the reference application and according to MPEP 2144.05, in the case where the claimed ranges overlap or lie inside ranges disclosed by the prior art a prima facie case of obviousness exists.
Therefore, claims 1, 3-6, 8, 13, 14, 19, and 22-29 of this application are unpatentable over claims 1-8, 11, and 12 of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 7, 9, and 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 11, and 12 of copending Application No. 17/625,955 (reference application) in view of Fischer and Wang as applied to claims 1, 3-6, 8, 13, 14, 19, and 22-29 above, and further in view of Hessler. Although the claims at issue are not identical, they are not patentably distinct from each other for reasons that follow.
This provisional rejection has been modified from its previous version in order to address applicant’s amendment to the claims.
The claims of the reference application do not recite the limitations of claims 7, 9, and 10 of this application.
Hessler generally teaches a multiphase biomaterial that is based on BNC (paragraph [0001]), which are suitable for a broad range of applications due to highly versatile determinable structures and material properties (paragraph [0002]) without requiring disadvantageous additives or composite formations produced in the synthesis with them (paragraph [0003]).
Regarding claim 7, Hessler teaches the multiphase biomaterial comprises layered phases (paragraphs [0022] and [0023]).
Regarding claim 9, Hessler teaches a plurality of bacterial cellular networks that form a homogenous phase system (paragraph [0023]).
Regarding claim 10, Hessler summarizes methods for modifying homogeneous or multi-phase biomaterials based on BNC (beginning at paragraph [0004]) teaching that teaches carboxymethyl cellulose (CMC) and methyl cellulose (MC) effect the pore size of the BNC network (paragraph [0007]).
In view of the teachings of Hessler, it would have been obvious to one of ordinary skill in the art for the BNC multiphase biomaterial of the claims of the reference application to have layered phases (claim 7), form a homogenous phase system (claim 9), and to alter pore size by adding CMC and MC (claim 10). One would have been motivated to and would have had a reasonable expectation of success to do so because of the teachings of Hessler regarding a multiphase biomaterial that is based on BNC.
Therefore, claims 7, 9, and 10 of this application are unpatentable over claims 1-8, 11, and 12 of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
RESPONSE TO REMARKS: Applicant argues the provisional rejections do not apply to the amended claims for the same reasons that the amended claims are non-obvious over the cited prior art.
Applicant’s arguments are not found persuasive. For the reasons set forth above, the amended claims of this application are unpatentable over claims 1-8, 11, and 12 of the reference application.
Conclusion
Status of the claims:
Claims 1, 3-10, 13, 14, 19, and 22-29 are pending.
Claims 1, 3-10, 13, 14, 19, and 22-29 are rejected.
No claim is in condition for allowance.
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/David Steadman/Primary Examiner, Art Unit 1656
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