DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/22/2026 has been entered.
Claims 1-2, 7-14 and 16-21 are pending in this application.
Applicant’s amendment to the claims filed 06/22/2026 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed on 06/22/2026 in response to the final rejection mailed on 01/21/2026 are acknowledged and have been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The elected subject matter is
Invention I, corresponding to claims 1-2, 7-14, 16-18 and 21, drawn to a method of increasing vitamin B-12 by administering a microbial composition,
elected in the reply filed on 08/03/2024.
Claims 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. The election was made with traverse in the reply filed 08/03/2024.
Claim Objections
Claim 21 is objected to for the typos in “Lactobacilli fermentum”, “Lactobacilli plantarum”, “Lactobacilli rhamnosus”, “Lactobacilli casei”, Lactobacilli reuteri”, “Lactobacilli gasseri”, “Streptococcus Salivarius”, and “Streptococci thermophilus”. In the interest of improving claim form, Applicant should consider an amendment to recite species names in lower case, and use the genus names of “Lactobacillus” and “Streptococcus” where appropriate.
Claim Rejections - 35 USC § 112(b)
Claim 21 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor regards as the invention.
The instant rejection is maintained from the previous Office Action.
Claim 21 is indefinite for the phrase “a composition comprising at least two strains of bacteria … wherein the at least one strain of bacteria of the at least two strains comprises Propionibacterium freudenreichii UF … wherein the at least one strain of bacteria of the at least two strains of bacteria comprises at least a second strain of bacteria”, as it is unclear whether the claims require at least one strain of bacteria or at least two strains of bacteria.
Response to Remarks: beginning on page 5 of Applicant’s response to rejections under 35 USC 112(b); Applicant in summary contends the amendments to the claims obviate the 112(b) rejections of record.
Applicant’s remarks are considered and found not convincing. The amendments to claim 21 do not overcome the 112b rejection for the reasons stated above.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 12 is newly rejected under 35 U.S.C. 112(d) as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
The instant rejection is newly stated and necessitated by claim amendment.
Claim 12 recites “the method of claim 1, wherein the administration of the composition increases the subject’s serum B12 levels by at least 10% relative to the subject’s serum B12 level prior to administration of the composition”, while claim 1 already recites “wherein the serum vitamin B12 levels of the subject increase by at least 10% relative to the serum B12 levels of the subject prior to administration of the composition”. Therefore claim 12 does not further limit claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
The rejection of claims 1-2, 11, 13 and 16-17 under 35 U.S.C. 103 as being unpatentable over Li et al. (PNAS, 2020, vol 117(1): 602-609; cited on the IDS submitted 08/03/2023; herein referred to as Li) in view of Ge et al. (Mucosal Immunity, 2019, vol 12:434-444; cited on the IDS submitted 08/03/2023; herein referred to as Ge),
the rejection of claims 7-8 under 35 U.S.C. 103 as being unpatentable over Li in view of Ge, and further in view of Bernardeau et al. (J Appl Microbiol, 2001, vol 91:1103-1109; cited on the Form PTO-892 mailed 12/13/2023; herein referred to as Bernardeau),
the rejection of claims 9-10 under 35 U.S.C. 103 as being unpatentable over Li in view of Ge, and further in view of Nataraj et al. (Microb Cell Fact, 2020, v 19:168-189; cited on the Form PTO-892 mailed 12/13/2023; herein referred to as Nataraj),
the rejection of claim 14 under 35 U.S.C. 103 as being unpatentable over Li in view of Ge, and further in view of Brasili et al. (J Nutrition, 2013, v 143(10):1549-1557; cited on the Form PTO-892 mailed 12/23/2023; herein referred to as Brasili),
the rejection of claim 18 under 35 U.S.C. 103 as being unpatentable over Li in view of Ge, and further in view of Torow et al. (J Immunol, 2017, vol 198(2):557-563; cited on the Form PTO-892 mailed 12/13/2023; herein referred to as Torow), and
the rejection of claim 21 under 35 U.S.C. 103 as being unpatentable over Li in view of Ge, Bernardeau and Nataraj
are withdrawn in view of the amendment to claim 1 to recite “wherein the serum vitamin B12 levels of the subject increase by at least 10% relative to the serum vitamin B12 levels of the subject prior to administration of the composition”.
Claims 1-2, 11-13 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Ge and Woodard et al. (J Gastrointest Surg, 2009, v 13:1198-1204; cited on the Form PTO-892 mailed 12/13/2023; herein referred to as Woodard).
The instant rejection is maintained from the previous office action.
Claim 1 is drawn to a method for increasing vitamin B12 levels in a subject comprising administering to the subject a composition comprising: at least one strain of bacteria, wherein the at least one strain of bacteria comprises Propionibacterium freudenreichii UF (UF1), and wherein the composition administered delivers a dose of UF1 to the subject from 5 x 109 to 1 x 1010 colony forming units (CFU),
wherein the serum vitamin B12 levels of the subject increase by at least 10% relative to the serum vitamin B12 levels of the subject prior to administration of the composition.
Li discusses regulating Vitamin B12 (VB12) biosynthesis in Propionibacterium strain UF1 [title].
Regarding claim 1 and the limitation of increasing VB12 levels and a strain of bacteria comprising Propionibacterium freudenreichii UF1, Li teaches that VB12 is provided by some gut microbes through fermentation of complex carbohydrates, as VB12 is a crucial cofactor for critical enzymes [p 602, col 1, para 1-2]. Li further teaches UF1 is a probiotic [p 602, col 2, para 1] that produces VB12 [abstract], and that probiotics are known to benefit the host when administered in adequate amounts [p 608, col 1, para 2].
Li does not teach the administration of UF1 or the dosage of 5 x 109 to 1 x 1010 CFU and the increase in serum VB12 of at least 10% compared to the subject prior to administration.
Ge discusses the neonatal intestinal immune regulation by Propionibacterium UF1 [title], and describes the administration of UF1 to newborn mice and its acceleration of neonatal protection against intestinal infection [p 434, col 2, para 2].
Regarding claim 1, Ge teaches the administration of UF1 at doses of 109 CFU to neonatal mice [p 440, col 2, para 2], which is considered to encompass the claimed lower end dosage of 5 x 109 CFU, and MPEP 2144.05.I states In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. Additionally, as stated in MPEP 2144.05(I), a prima facie case of obviousness exists where the claimed ranged or amounts do not overlap with the prior art but are merely close.
Furthermore, MPEP 2144.05(II)(B) sets forth that the differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence suggesting that such concentration is critical, as MPEP 2144.05(B) states "[W]here 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). As Ge provides a motivation for increasing the dosage of UF1 for enhanced effect as well as the disclosure that the dosage of bacteria is a result-effective variable in the teaching “it may be of significance if mothers and newborn mice would be continuously gavaged with P. UF1 to increase the enhancement of T cell immunity in newborn mice” [p 435, col 1, para 1] as well as the teaching that newborn mice that were continuously gavaged with UF1 showed a clearly enhanced frequency of Th17 cells [p 438, col 2, final paragraph; also shown in Figure 2A and Figure 2C], it would have been considered mere routine experimentation to identify the optimum or workable concentration range of the result-effective variable to achieve the desired results.
Woodard discusses the results of probiotics given to surgery patients [title], wherein it is described that potential mediators to the gut microbiota, which perform symbiotic digestive and metabolic functions within the human GI tract, are considered to be safe therapy, and have been effective treatment for infective gastroenteritis, irritable bowel syndrome, general inflammation, preventing and treating acute respiratory infections and urogenital infection [p 1199, col 1, paras 2-3].
Regarding the limitation “wherein the serum vitamin B12 levels of the subject increase by at least 10%...” in claim 1, Woodard teaches that the administration of probiotics comprised of Lactobacillus species [p 1201, col 1, para 2] to post-surgical patients resulted in an increase of B12 from preoperative levels of 668 pg/ml to 1215 pg/ml after three months [Table 3] as a result of serology analysis [p 1201, col 1, para 1].
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine Li and Ge by using the UF1 of Li with the administration method and dosages of Ge to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to combine the elements of Li and Ge, because Li teaches that UF1 produces VB12, and Ge teaches the administration dosage of UF1 conveys the acceleration of neonatal protection against intestinal infection in neonatal mice. One of ordinary skill in the art would have had a reasonable expectation of success because Li and Ge discuss the health benefits of the probiotic UF1 bacterial strain.
In view of Woodard, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Li and Ge by including the probiotic comprised of Lactobacillus species, as taught by Woodard, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Li and Ge by including the probiotic of Woodard in the composition, because Woodard teaches that three months of administering a Lactobacillus-containing probiotic resulted in an 81.88% increase in serum B12 levels compared to before administration. One of ordinary skill in the art would have had a reasonable expectation of success because Woodard teaches the increase in serum B12 levels upon administration of Lactobacillus probiotics, and Le and Ge discuss administration of UF1 probiotics known to synthesize B12 and their associated health benefits.
Regarding claims 2 and 11, Li teaches that UF1 is a probiotic [p 602, col 2, para 1].
Regarding claim 12, claim 12 does not further limit claim 1 as stated in the rejection under 35 USC 112(d) above, therefore the rejection of claim 12 is included in the rejection of claim 1.
Regarding claim 13, Ge teaches the significant increase in Th17 cells over time with UF1 treatment [Figure 1C].
Regarding claim 16-17, Ge teaches “it may be of significance if mothers and newborn mice would be continuously gavaged with P. UF1 to increase the enhancement of T cell immunity in newborn mice” [p 435, col 1, para 1], which is interpreted to be comparative to newborn mice without administration of UF1.
Therefore, the invention of claims 1-2, 11-13 and 16-17 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 7-8 are newly rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Ge and Woodard as applied to claims 1-2, 11-13 and 16-17 above, and further in view of Bernardeau et al. (J Appl Microbiol, 2001, vol 91:1103-1109; cited on the Form PTO-892 mailed 12/13/2023; herein referred to as Bernardeau).
The instant rejection is newly recited and necessitated by claim amendment.
Claim 7 is drawn to the method of claim 1, wherein the dose of UF1 is from 1 x 109 to about 2 x 1010 AFU.
The combined teachings of Li, Ge and Woodard as applied to claims 1-2, 11-13 and 16-17 are discussed above. These references do not teach dosages in Active Fluorescent Units (AFU).
Bernardeau discusses the usefulness of epifluorescence for quantitative analysis of lactobacilli in probiotic feed [title], wherein methods are described for the distinction between living and dying cells [p 1103, col 2, para 2] as well as the quantification of alive but not culturable (ABNC) microorganisms [p 1103, col 2, para 3] that include the determination of active fluorescence units (AFU) within a product [p 1104, col 1, para 1].
Regarding claims 7-8 and the limitation of AFU, Bernardeau teaches that methods of epifluorescence are important for the quantification of ABNC because some probiotic features are linked with the viability properties of cells, and therefore the ability to culture bacteria from probiotic product cannot be used as the sole indicator of the probiotic capabilities of functional food products [p 1104, col 1, para 1]. As Ge teaches that UF1 can be cultured in MRS medium [p 440, col 1, para 2], and Bernardeau teaches that epifluorescence is an alternative viable cell quantitation to culturing bacteria, one of skill in the art would recognize that the AFU ranges of the claimed composition comprising UF1 would be the same as the CFU ranges disclosed by Ge and discussed in the above rejection of claim 1.
In view of Bernardeau, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention modify the combined method of Li, Ge and Woodard by using the dosages of bacteria as determined by the method of Bernardeau to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Li, Ge and Woodard, because Bernardeau teaches that probiotic features are linked with the viability properties of cells, and therefore the ability to culture bacteria from probiotic product cannot be used as the sole indicator of the probiotic capabilities of functional food products. One of ordinary skill in the art would have had a reasonable expectation of success because Li, Ge and Bernardeau discuss the health benefits of probiotic bacteria.
Therefore, the invention of claims 7-8 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 9-10 are newly rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Ge and Woodard as applied to claims 1-2, 11-13 and 16-17 above, and further in view of Nataraj et al. (Microb Cell Fact, 2020, v 19:168-189; cited on the Form PTO-892 mailed 12/13/2023; herein referred to as Nataraj).
The instant rejection is newly recited and necessitated by claim amendment.
Claim 9 is drawn to the method of claim 1, wherein the UF1 is a mixture of probiotic and parabiotic.
Parabiotic is defined in the instant specification as a product comprising killed or inactivated microbes that may positively affect subject health.
The combined teachings of Li, Ge and Woodard as applied to claims 1-2, 11-13 and 16-17 are discussed above. These references do not teach that the UF1 is a mixture of probiotic and parabiotic.
Nataraj reviews postbiotics and parabiotics for their uses in microbial biotherapy and functional foods [title], and describes the use of postbiotics and parabiotics to provide the health benefits of probiotics without the limitations of viability controls [abstract].
Regarding claim 9, Nataraj teaches examples of parabiotics wherein inactivated/dead/nonviable microbial cells of probiotics are either intact or ruptured containing cell components such as teichoic acids, peptidoglycan-derived muropeptides, surface protruding molecules (pili, fimbriae, flagella), polysaccharides such as exopolysaccharides, cell surface-associated proteins, and cell wall-bound biosurfactants [p 170, col 1, para 4 to col 2, para 1]. Nataraj further teaches the use of said non-viable parabiotic bacteria for anti-adhesion potential, immunomodulatory and gut barrier function; and the use of metabolites such as biosurfactants and organic acids for antagonistic knack against enteropathogens and nutrition and anti-oxidant properties [Figure 1].
In view of Nataraj, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Li, Ge and Woodard by adding parabiotic bacteria, as taught by Nataraj, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Li, Ge and Woodard by using parabiotic UF1, because Nataraj teaches that non-viable parabiotic bacteria have utility for anti-adhesion potential, immunomodulatory and gut barrier function. One of ordinary skill in the art would have had a reasonable expectation of success because Li, Ge and Nataraj discuss the health benefits of probiotic bacteria.
Regarding claim 10, Nataraj further teaches the use of said non-viable parabiotic bacteria for anti-adhesion potential, immunomodulatory and gut barrier function; and the use of metabolites such as biosurfactants and organic acids for antagonistic knack against enteropathogens and nutrition and anti-oxidant properties [Figure 1].
Therefore, the invention of claims 9-10 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 14 is newly rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Ge and Woodard as applied to claims 1-2, 11-13 and 16-17 above, and further in view of Brasili et al. (J Nutrition, 2013, v 143(10):1549-1557; cited on the Form PTO-892 mailed 12/23/2023; herein referred to as Brasili).
The instant rejection is newly recited and necessitated by claim amendment.
Claim 14 is drawn to the method of claim 1, wherein the administration of the composition increases the levels of NAD+ and/or NMN in the subject.
NAD+ and NMN are known in the art as the cofactor-related molecules nicotinamide adenine dinucleotide and nicotinamide mononucleotide, respectively.
The combined teachings of Li, Ge and Woodard as applied to 1-2, 11-13 and 16-17 are discussed above. These references do not teach increases of NAD+ and/or NMN levels upon administration.
Brasili discusses the metabolic profiles induced in mice by Lactobacillus acidophilus and Bifidobacterium lactis as determined by H-NMR [title], wherein it is described that the dietary manipulation of the gut microbiota through probiotic supplementation can improve or restore a healthy microbial community and induce several benefits [p 1550, col 1, para 2].
Regarding claim 14, Brasili teaches that treatment of mice with L. acidophilus and B. lactis resulted in decreased N-methylnicotinamide (Mnam) concentration, which based on the concurrent reduction in nicotinamide (Nam) suggested enhanced utilization of Nam towards NAD synthesis [p 1555, col 1, para 2]. Here again, it is to be noted that the method of claim 1 does not exclude the presence of additional strains of bacteria because of the transitional phrase “comprising at least one strain”.
In view of Brasili, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Li, Ge and Woodard by including in the mixture the probiotics L. acidophilus and B. lactis, as taught by Brasili, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Li, Ge and Woodard by including the probiotics of Brasili, because Brasili teaches that the dietary manipulation of the gut microbiota through probiotic supplementation can improve or restore a healthy microbial community and induce several benefits. One of ordinary skill in the art would have had a reasonable expectation of success because Brasili, Le, and Ge all discuss the health effects of probiotics.
Therefore, the invention of claim 14 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 18 is newly rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Ge and Woodard as applied to claims 1-2, 11-13 and 16-17 above, and further in view of Torow et al. (J Immunol, 2017, vol 198(2):557-563; cited on the Form PTO-892 mailed 12/13/2023; herein referred to as Torow).
The instant rejection is newly recited and necessitated by claim amendment.
Claim 18 is drawn to the method of claim 17, wherein the infant was born preterm.
The combined teachings of Li, Ge and Woodard as applied to claims 1-2, 11-13 and 16-17 are discussed above. These references do not teach administration to preterm infants.
Torow reviews the effects of the enteric microbiota on the innate and adaptive immune system following periods after birth [abstract].
Regarding claim 18, Torow teaches that there is a downside to preventing infectious disease burden on newborns, in that there is a need to compensate for the lack of microbial exposure during early development without the risk for potential life-threatening infections, and that facilitating exposure of children to benign nonpathogenic microbes can be a solution, such as the administration of probiotic bacteria to preterm neonates [p 562, col 1, para 1].
In view of Torow, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Li, Ge and Woodard by including administration to preterm infants, as taught by Torow, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Li, Ge and Woodard administering to preterm infants, because Torow teaches that facilitating exposure of children to benign nonpathogenic microbes can increase microbial exposure during early development without the risk of like-threatening infection. One of ordinary skill in the art would have had a reasonable expectation of success because Torow, Li and Ge all discuss the health effects of probiotic administration.
Therefore, the invention of claim 18 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 21 is newly rejected under 35 U.S.C. 103 as being unpatentable over Li in view of Ge, Woodard, Bernardeau and Nataraj.
The instant rejection is newly recited and necessitated by claim amendment.
Claim 21 is drawn to a method for increasing vitamin B12 levels in a subject comprising administering to the subject a composition comprising:
at least two strains of bacteria wherein the at least one strain of bacteria of the at least two strains of bacteria comprises UF1 and wherein the composition administered delivers a dose of UF1 to the subject from 5 x 109 to 1 x 1010 Active Fluorescent Units (AFU),
wherein the at least one strain of bacteria of the at least two strains of bacteria comprises at least a second strain of bacteria consisting essentially of: Propionibacterium acnes, Propionibacterium avidum, Propionibacterium granulosum, Propionibacterium lymphophilum, Propionibacterium acidiproprionic, Propionibacterium jensenii, Propionibacterium thoenii, lactic acid bacteria including Lactobacillus acidophilus, Lactobacilli fermentum, Lactobacilli plantarum, Lactobacilli rhamnosus, Lactobacilli casei, Lactobacilli reuteri, Lactobacilli gasseri and Streptococcus salivarius, Streptococci thermophilus, spore forming bacteria including Bacillus coagulans, Bacillus subtilis, bifidobacteria, yeast-derived bacteria including Saccharomyces boulardii, and/or mixtures of the foregoing,
wherein the serum vitamin B12 levels of the subject increase by at least 10% relative to the serum vitamin B12 levels of the subject prior to administration of the composition.
In view of the indefiniteness of claim 21 set forth above, and for the sake of compact prosecution, the claim is being interpreted as requiring two separate strains of bacteria, one being UF1 and another being selected from the Markush group set forth in the claim.
The teachings of Li, Ge, Woodard and Bernardeau are discussed above, and include the administration of UF1 to increase Vitamin B12 levels in subject at dosages of 5 x109 to 1 x 1010 AFU as discussed in the rejection of claims 7-8, and the increase in serum B12 of 10% as discussed in the rejection of claim 1. These references do not teach a second strain of bacteria comprising those listed in the claim.
Nataraj reviews postbiotics and parabiotics for their uses in microbial biotherapy and functional foods [title], and describes the use of postbiotics and parabiotics to provide the health benefits of probiotics without the limitations of viability controls [abstract].
Regarding claim 21, Nataraj teaches lactic acid bacteria cultures such as Lactobacillus fermentum that synthesize EPS provide the health benefits of anti-biofilm effects against the pathogens L. monocytogenes, E. faecalis, S. aureus, P. aeruginosa, and Salmonella spp., and that using mixtures of Lactobacillus paracasei and Lactobacillus plantarum provide the benefit of immunomodulation [Table 1]. One of skill in the art would therefore be motivated to add an additional strain to the composition of Li and Ge, because Nataraj teaches the above strains provide the health benefits of immunomodulation.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine Li, Ge, Woodard, Bernardeau and Nataraj by using the UF1 of Li with the administration method and dosages of Ge as determined by the method of Bernardeau to obtain 10% increases in serum B12 levels as taught by Woodard, and by adding a second strain as taught by Nataraj to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to combine the elements of Li, Ge, Woodard, Bernardeau and Nataraj, because Li teaches that UF1 produces VB12, Ge teaches the administration dosage of UF1 conveys the acceleration of neonatal protection against intestinal infection in neonatal mice, Woodard teaches that three months of administering a Lactobacillus-containing probiotic resulted in an 81.88% increase in serum B12 levels compared to before administration, Bernardeau teaches that probiotic features are linked with the viability properties of cells, and therefore the ability to culture bacteria from probiotic product cannot be used as the sole indicator of the probiotic capabilities of functional food products, and Nataraj teaches lactic acid bacteria cultures when administered in mixtures with other strains can provide a benefit of immunomodulation. One of ordinary skill in the art would have had a reasonable expectation of success because Li, Ge, Woodard, Bernardeau and Nataraj discuss the health benefits of probiotic bacteria.
Therefore, the invention of claim 21 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to Remarks: Beginning on page 5 of Applicant’s response to the 35 U.S.C. 103 rejections; Applicant in summary contends Ge does not teach the recited dose of bacteria, as the values are not close in accordance with MPEP 2144.05.I, and the 5-fold difference in dosage being minor is not supported by prior art; Applicant further contends the different standard of measurement provided by Examiner does not encompass the claimed range; Applicant further contends Ge indicates a continuous dosage to mothers rather than an increase in the size of the dose, and therefore there is no motivation to optimize the dose of Ge; Applicant further contends neither Li nor Ge teach the increase in vitamin B12 levels recited in the claims as amended.
Applicant’s remarks are considered and found not convincing.
Regarding the assertion that Ge does not teach the recited dose of bacteria, as the values are not close in accordance with MPEP 2144.05.I, and the 5-fold difference in dosage being minor is not supported by prior art: Ge teaches a dosage of 109 CFU, without disclosing any mantissa, and therefore the dosage of Ge teaches a dosage in the log10 range of 9. This broad teaching of Ge encompasses a portion of the claimed dosage of 5 x 109 to 1 x 1010 CFU.
Additionally, considering an interpretation where the dosage of Ge is restricted to 1 x 109 CFU, which appears to be Applicant’s argument based on the statement that difference in dosage is 5-fold, the previous Office action cited Corry et al. (Food Microbiol, 2007, 24:230; cited on the Form PTO-892 mailed 01/21/2026) to emphasize the acceptable variation in CFU numbers common in the field of microbiology, which is not a different standard as stated by Applicant. Corry disclosed that CFU counts commonly contain variation within at best +/- 0.5 log10 [p 231, col 1, para 3], as well as different variations in CFU counts obtained by different methods that have 95% CI ranges as large as 1.27 log10 and 1.8 log10 [p 434, col 1, para 3], further emphasizing the variation understood to be associated with reports of CFU. Applicant contends even with the 0.5 log10 variation in CFU, the range of Ge interpreted by Applicant is outside of the claimed range of 5 x 109 CFU, as Applicant states the upper bound is 9.5. However this is not how variations in log10 are applied. For example, Applicant’s calculation of the log-10 value of 5 x 109 is correctly stated as 9.699. Therefore the variation in said log-10 value, considering the most conservative variation disclosed by Corry of +/- 0.5 log10, would correspond to log10 values of 9.199 to 10.199, and therefore the claimed value 5 x 109 CFU would correspond to a variation of 1.58 x 109 to 1.58 x 1010 CFU (109.199 to 1010.199). The same variation applied to Applicant’s interpretation of Ge would be 3.16 x 108 to 3.16 x 109 CFU. Therefore these ranges are overlapping, even when only considering the most conservative variation disclosed by Corry, and only considering the interpretation of Ge wherein the mantissa of 109 CFU is 1. Therefore the dosage of Ge is considered to encompass the claimed dosage of 5 x 109 CFU.
Additionally, considering an interpretation that the dosage of Ge does not overlap with the claimed range, the dosage of Ge is considered to be close based on the broadness of the teaching of Ge. As stated previously, MPEP 2144.05(II)(B) sets forth that the differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence suggesting that such concentration is critical, as MPEP 2144.05(B) states "[W]here 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). Applicant has not provided evidence that the recited concentration is critical.
Regarding the assertion that Ge indicates a continuous dosage to mothers rather than an increase in the size of the dose, and therefore there is no motivation to optimize the dose of Ge: While Ge does teach continuous gavage to be beneficial to mothers (and also newborns, see Figures 2A and 2C of Ge), one of ordinary skill in the art would have reasonably expected to conclude such continuous gavage corresponds to increased dosage frequency over time, and therefore increased dosage to the subject. This teaching constitutes a result-effective variable according to MPEP 2144.05.II.B, wherein the increased dosage results in beneficial effects on the mothers (and newborns). Considering an interpretation where Ge does not teach the claimed range of dosage, it would have been obvious to one of ordinary skill in the art to optimize the combined method to achieve the claimed dosage, because Ge teaches the increased dosage of UF1 results in beneficial effects on the mother and newborn.
Regarding the assertion that neither Li nor Ge teach the increase in vitamin B12 levels recited in the claims as amended: this feature of the claims is taught by Woodard, and is outlined in the rejection above.
Conclusion
Status of the Claims:
Claims 1-2, 7-14 and 16-21 are pending.
Claims 19-20 are withdrawn from consideration.
Claims 1-2, 7-14, 16-18 and 21 are rejected.
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 pm.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656
Prosecution Insights