DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 December 16, 2025, has been entered.
Claims 1-15, 17-19, 24, 29-31, 34, and 36 are cancelled. Claim 43 is new.
Claims 16, 20-23, 25-28, 32, 33, 35, and 37-43 are pending and examined on the merits.
Notice Re: Prior Art Available Under Both Pre-AIA and AIA
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 16, 20, 21, 23, 25-28, 32, 33, 35, and 39-43 are rejected under 35 U.S.C. 103 as being unpatentable over Langford (US 2010/0172876. Previously cited) in view of MacDonald (Molecular Genetics and Metabolism. 2011. 104: S55-S59. Previously cited).
Langford discloses a method of treating a person suffering from one of various conditions, including cow’s milk allergy and/or food protein intolerance, comprising administering to the person an effective amount of a composition comprising free amino acids as a sole source of protein, indigestible carbohydrates, and milk protein free Bifidobacteria (amongst other components) (claim 1 of Langford). The indigestible carbohydrates, i.e., non-digestible carbohydrates, are most preferably a mixture of long chain fructooligosaccharide (lcFOS) with an average DP between 10-60 and short chain fructooligosaccharide (scFOS) with an average DP between 3 and 10 (paragraph [0031]). Fructooligosaccharides are directed to indigestible fiber of instant claims 25, 26, and 35, and the mixture of lcFOS and scFOS meets the limitations of instant claims 39, 40, and 42. Also, the Bifidobacteria is directed to lactic acid producing bacterium, specifically meeting the lactic acid producing bacterium limitation of instant claim 20.
Regarding the amount of the mixture of lcFOS and scFOS (directed to the claimed indigestible fiber), an embodiment of the powdered formulation in accordance with the invention of Langford is disclosed in paragraph [0051]. The formulation comprises 4.1 g scFOS and 0.43 g lcFOS per 100 g powder. Therefore, the concentration of indigestible fiber (scFOS + lcFOS) is 4.53 wt.%, based on dry weight of the composition, which falls within the range of instant claim 16 [Calculation:
4.1
g
s
c
F
O
S
+
0.43
g
l
c
F
O
S
100
g
p
o
w
d
e
r
×
100
=
4.53
w
t
%
].
The person that is treated by the invention of Langford can be an infant in the age between 0 and 36 months (claim 2 of Langford). Therefore, the person treated by the invention of Langford can be an infant or a toddler since the infant age range includes ages for toddlers (e.g. 24 months). The composition that is administered to infants (as defined in Langford, includes toddlers) is referred to as an amino acid based formula (paragraph [0001]).
Langford teaches that the composition that is administered preferably can be used to improve the stool characteristics of infants suffering from any of the above mentioned conditions (paragraph [0058]). Also, Langford recognizes that in the intestine of infants receiving amino acid based foods, instead of the bifidobacteria and lactobacilli dominant flora in normal infants receiving breast milk, many other bacterial species, including potentially pathogenic species, may prevail in the intestine of infants receiving amino acid based foods (paragraph [0010]). In view of this, Langford recognized the criticality of a beneficial flora development in infants receiving a diet containing mainly free amino acid as a protein source (paragraph [0012]). Further still, Langford found that a specific selection of dietary oligosaccharides, preferably fructans and/or pectin degradation products, can be beneficially added to the elemental formula to stimulate the flora development without causing any allergic side effects (paragraph [0013]). Therefore, improving the stool characteristics of the infant of Langford is directed to treating an infant or toddler suffering from dysbiosis in the intestinal microbiota, as the need for improvement in stool characteristics signifies that there is dysbiosis in the intestinal microbiota based on the discussion in paragraphs [0010], [0012], and [0013] of Langford, thereby meeting limitations of the claimed invention. Also, based on paragraphs [0010], [0012], and [0013], improving the stool characteristics of the infants is directed to normalizing the intestinal microbiota in the amino acid based formula fed infant or toddler, comprising increasing the proportion of lactic acid producing bacteria (the beneficial flora that includes bifidobacteria and lactobacilli directed to lactic acid producing bacteria), thereby meeting limitations of the claimed invention.
Additionally, Langford teaches that the composition of the amino acids in their formula preferably comprises all essential amino acids except for patients with phenylketonuria (PKU) (paragraph [0043]). PKU is a disorder of the amino acid metabolism of instant claim 32. Since Langford teaches patients with PKU for practice of their invention, then it would have been prima facie obvious to the skilled artisan to practice the invention of Langford discussed above (treating an infant or toddler suffering from a condition, e.g., cow’s milk allergy and/or food protein intolerance, used to improve stool characteristics of the infant or toddler) on an infant or toddler having PKU. In doing so, then the infant or toddler is directed to an infant or toddler having a disorder of amino acid metabolism (PKU). Since the formula does not comprise all essential amino acids for the patient with PKU, then the formula that is administered is directed to a nutritional composition that is depleted from the amino acid(s) that the infant or toddler having the disorder of amino acid metabolism (PKU) cannot metabolize, meeting limitations of the claimed invention. Note further that the free amino acids disclosed for the composition (claim 4 of Langford) do not include phenylalanine.
In sum, Langford meets limitations of the claimed invention since it renders obvious a method for normalizing the intestinal microbiota in an amino acid-based formula-fed infant or toddler having a disorder of amino acid metabolism (PKU), comprising administering an effective amount of a nutritional composition (their composition) comprising an amino-acid-based formula supplemented with indigestible fiber (mixture of lcFOS and scFOS) and a lactic acid producing bacterium (Bifidobacteria) to the infant or toddler having the disorder of amino acid metabolism, which infant or toddler suffers from a dysbiosis in the intestinal microbiota and which method comprises increasing the proportion of lactic acid producing bacteria (the beneficial flora that includes bifidobacteria and lactobacilli directed to lactic acid producing bacteria), wherein the nutritional composition is depleted for the amino acid(s) that the infant or toddler having the disorder of amino acid metabolism cannot metabolize, and, wherein the composition of indigestible fiber is 4.53 wt.%, based on the dry weight of the composition (falling within the claimed range).
Langford differs from the claimed invention in that Langford does not expressly disclose that their method comprises decreasing the proportion of Clostridium bacteria in the intestinal microbiota of the amino acid-based formula fed infant or toddler.
As pointed out above, Langford recognizes that in the intestine of infants receiving amino acid based foods, instead of the bifidobacteria and lactobacilli dominant flora in normal infants receiving breast milk, many other bacterial species, including potentially pathogenic species, may prevail in the intestine of infants receiving amino acid based foods (paragraph [0010]). In view of this, Langford recognized the criticality of a beneficial flora development in infants receiving a diet containing mainly free amino acid as a protein source (paragraph [0012]). Further still, Langford found that a specific selection of dietary oligosaccharides, preferably fructans and/or pectin degradation products, can be beneficially added to the elemental formula to stimulate the flora development without causing any allergic side effects (paragraph [0013]).
MacDonald discloses that infants with moderate to severe Phenylketonuria (PKU) receive up to 75% of their protein requirements (excluding phenylalanine), along with an equivalent percentage of their vitamins and minerals, from their infant phenylalanine-free protein substitute (IPS) (page S55, first paragraph). MacDonald investigated the tolerability and efficacy of an IPS with prebiotics, including evaluating any effects on GI microbiota of infants with PKU (page S56, left column, fourth paragraph). In the study, infants diagnosed with PKU were administered the infant protein substitute containing short-chain galactooligosaccharides (scGOS) and long-chain fructooligosaccharides (lcFOS) (page S56, left column, last three paragraphs; page S57, left column, last paragraph). In the study, MacDonald points out that the IPS with prebiotics (PB) replaced the previous IPS without prebiotics (PB) (page S56, left column, last paragraph). MacDonald assessed the dominant bacterial groups in stool samples of the infants in the study (page S56, right column, first paragraph). MacDonald found that the infant who recorded the highest concentrations of Clostridium histolyticum/lituseburense and enterobacteriaceae at baseline was receiving the infant formula without prebiotics prior to the study, and showed a marked decrease in both groups at Week 8 accompanied by a marked increase in bifidobacterial (page S57, left column, fourth paragraph). These bacteria (Clostridium histolyticum/lituseburense) are potential pathogens (page S57, right column, first paragraph).
Before the effective filing date of the claimed invention, in improving the stool characteristics of the infant of toddler, it would have been obvious to the person of ordinary skill in the art that the proportion of Clostridium bacteria is decreased in the intestinal microbiota of the amino acid-based formula fed infant or toddler when performing the method rendered obvious by Langford. Since the beneficial flora (bifidobacteria and lactobacilli flora) development is increased, then the proportion of potentially pathogenic species is decreased. The person of ordinary skill in the art would have expected that the decrease in proportion of potentially pathogenic species includes the decrease in proportion of Clostridium bacteria (e.g., Clostridium histolyticum/lituseburense) since they are pathogenic bacteria present in the stool of infants with PKU which are decreased when there is an increase in bifidobacteria, as indicated in MacDonald. Moreover, since Langford renders obvious improving stool characteristics of an amino acid-based formula-fed infant or toddler having a disorder of amino acid metabolism (PKU) comprising administering an effective amount of a composition directed to the claimed nutritional composition of instant claim 16, then the claimed effects as recited in instant claim 16, including decreasing the proportion of Clostridium bacteria in the intestinal microbiota of the amino acid-based formula fed infant or toddler, would have necessarily occurred. In administering the same composition to the same subject as claimed by performing the method rendered obvious by Langford in view of MacDonald, then the same effects as claimed necessarily occur.
Therefore, Langford in view of MacDonald renders obvious instant claims 16, 20, 25 (fructooligosaccharide), 26 (at least fructooligosaccharides), 32 (phenylketonuria), 39, 40 (scFOS directed to ‘short chain oligosaccharide,’ lcFOS directed to ‘long chain oligosaccharide’), and 42.
Regarding instant claim 21, Langford teaches that preferably the bifidobacteria is Bifidobacterium breve (paragraph [0040]). Thus, instant claim 21 is rendered obvious.
Regarding instant claim 23, Langford teaches a nutritionally complete powdered formulation of their invention that comprises 1 x 1010 CFU of Bifidobacterium breve, 4.1 g scFOS, and 0.43 g lcFOS per 100 g powder (paragraph [0051]). Therefore, the concentration of lactic acid producing bacterium (B. breve) is 2.2 × 109 CFU lactic acid producing bacterium per gram indigestible fiber which falls within the claimed range [Calculation:
1
×
10
10
C
F
U
B
.
b
r
e
v
e
4.1
g
s
c
F
O
S
+
0.43
g
l
c
F
O
S
=
2.2
×
10
9
C
F
U
p
e
r
g
]. Thus, instant claim 23 is rendered obvious.
Regarding instant claim 35, Langford discloses that free amino acids are the sole source of protein in their composition (claim 1 of Langford). Therefore, the protein source of the amino acid-based formula of the composition of Langford (directed to nutritional composition) comprises 100 wt.% free amino acids, which falls within the claimed range of at least 95 wt.% free amino acids. As discussed above with respect to instant claim 21, Langford teaches B. breve in their composition. As discussed above with respect to instant claim 23, Langford teaches 2.2 × 109 CFU lactic acid producing bacterium per gram indigestible fiber; this falls within the range of instant claim 35. Therefore, instant claim 35 (at least fructooligosaccharides as the indigestible fiber) is rendered obvious.
Regarding instant claim 41, Langford teaches that the mixture of lcFOS and scFOS is preferably in a ratio of 1:9 in their composition (paragraph [0031]). Therefore, the amount of short chain oligosaccharide (scFOS) in their composition (directed to nutritional composition) is greater than the amount of long chain oligosaccharide (lcFOS). As such, instant claim 41 is rendered obvious.
Regarding instant claim 43, Langford discloses a mixture of long chain fructooligosaccharide (lcFOS) with an average DP between 10-60 and short chain fructooligosaccharide (scFOS) with an average DP between 3 and 10 in their composition (paragraph [0031]). Therefore, instant claim 43 is rendered obvious.
Regarding instant claims 27, 28, and 33, Langford teaches that the composition that is administered further comprises a fatty acid source comprising long chain polyunsaturated fatty acids (claim 1 of Langford). The fatty acid source meets the lipid source limitations of instant claims 27 and 28. Additionally, Langford discloses that the long chain polyunsaturated fatty acid (LC-PUFA) composition comprises docosahexaenoic acid (DHA) and arachidonic acid (AA) (paragraphs [0047] and Table 3 on page 3). Therefore, instant claims 27, 28, and 33 (DHA, AA) are rendered obvious.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over Langford and MacDonald as applied to claims 16, 20, 21, 23, 25-28, 32, 33, 35, and 39-43 above, and further in view of Harthoorn (WO 2014/200351. Previously cited).
As discussed above, Langford in view of MacDonald renders obvious claims 16, 20, 21, 23, 25-28, 32, 33, 35, and 39-43. Langford teaches that preferably the bifidobacteria of their composition is Bifidobacterium breve (paragraph [0040]). However, Langford in view of MacDonald differs from claim 22 in that they do not expressly disclose that the Bifidobacterium breve is Bifidobacterium breve M-16V, as deposited with the Belgian Co-ordinated Collections of Microorganisms (BCCM) and designated LMG 23729.
Harthoorn discloses a nutritional composition comprising synbiotics for use in the treatment or prevention of infections in allergic patients (page 1, lines 4-5). The invention of Harthoorn is specifically intended for allergic infants and/or allergic toddlers (page 10, lines 25-26). The composition of Harthoorn comprises i) a protein source consisting of free amino acids, ii) at least one soluble indigestible fiber selected from the group consisting of fructooligosaccharides, non-milk derived fucosyloligosaccharides and polydextrose, and iii) at least one lactic acid bacterium selected from a group that includes Bifidobacterium breve (page 3, last paragraph). Most preferably the B. breve is B. breve M-16V (page 5, lines 22-27). Harthoorn points out that atopic infants have an altered gut microflora with increased Clostridia and decreased bifidobacteria (page 4, first paragraph). In Example 1, Harthoorn discloses studying the functional effects of an amino-acid based formula (AAF) with synbiotics (prebiotics and probiotics) in infants with cow’s milk allergy (CMA) (page 13, lines 18-20). The AAF is supplemented with milk protein free B. breve M-16V and a prebiotic fiber mix containing short chain fructooligosaccharides (scFOS) + long chain fructooligosaccharides (lcFOS) (page 13, lines 28 to page 14, line 4).
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art to substitute the Bifidobacterium breve of the method rendered obvious by Langford in view of MacDonald with Bifidobacterium breve M-16V for the predictable result of treating an infant or toddler suffering from any one of the conditions set forth in Langford that includes cow’s milk allergy and improving the stool characteristics of the infant or toddler. It would have been a matter to simple substitution of one known B. breve recognized for administration to an infant or toddler suffering from an allergy such as cow’s milk allergy, for another. Since Harthoorn discloses that it is preferred to include B. breve M-16V as the B. breve in a nutritional composition administered to an infant or toddler having an allergic condition (e.g. cow’s milk allergy) that comprises the same components as Langford (free amino acids as protein source; mixture of scFOS and lcFOS, Bifidobacteria), then the skilled artisan would have been motivated to include B. breve M-16V as the B. breve in the composition administered in the method rendered obvious by Langford in view of MacDonald in order to treat an infant or toddler having said allergic condition (e.g. cow’s milk allergy). There would have been a reasonable expectation of improving the stool characteristics of infants and toddlers by this substitution in the invention of Langford in view of MacDonald because Harthoorn included B. breve M-16V in their composition which stimulates the growth of Bifidobacteria and Lactobacilli in the intestine (page 8, second paragraph). Therefore, instant claim 22 is rendered obvious.
Claims 37 and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Langford and MacDonald as applied to claims 16, 20, 21, 23, 25-28, 32, 33, 35, and 39-43 above, and further in view of Hsu (US 2011/0091598. Previously cited).
As discussed above, Langford in view of MacDonald renders obvious claims 16, 20, 21, 23, 25-28, 32, 33, 35, and 39-43. The references differ from claim 37 in that they do not expressly disclose that the indigestible fiber (mixture of scFOS and lcFOS) in their nutritional composition has a solubility in water at 20ºC of at least 0.1 g/100 ml. The references further differ from claim 38 in that they do not expressly disclose that the indigestible fiber has a solubility in water at 20ºC of at least 0.1 g/100 ml.
Hsu discloses that fructooligosaccharide has a solubility in water at 25ºC of 75% (Table 1 on page 3). This converts to a solubility in water of 75 g/100 ml.
Before the effective filing date of the claimed invention, it would have been obvious to the person of ordinary skill in the art that the mixture of scFOS and lcFOS in the nutritional composition administered to the infant has a solubility in water at 20ºC that falls in the ranges of ‘at least 0.1 g/100 ml’ and ‘at least 0.5 g/100 ml’ in the method rendered obvious by Langford in view of MacDonald. Given the high solubility in water disclosed in Hsu for fructooligosaccharide at 25ºC, specifically much higher than 0.1 g/100 ml and 0.5 g/100 ml, then the skilled artisan would have expected that the scFOS and lcFOS of Langford in view of MacDonald have similar high solubilities in water at the similar temperature of 20ºC. Thus it would have been obvious to the skilled artisan that the scFOS and lcFOS have high solubilities in water at 20ºC that fall within the ranges of ‘at least 0.1 g/100 ml’ and ‘at least 0.5 g/100 ml’ of instant claims 37 and 38, respectively. As such, instant claims 37 and 38 are rendered obvious.
Response to Arguments
Applicant’s arguments, filed December 16, 2025, with respect to the rejection under 35 U.S.C. 103 of claims 16, 20-23, 25, 26, 32, 35, and 39-41 as being unpatentable over MacDonald in view of Harthoorn, the rejection under 35 U.S.C. 103 of claims 27, 28, and 33 as being unpatentable over MacDonald and Harthoorn in further view of Giovannini, the rejection under 35 U.S.C. 103 of claims 37 and 38 as being unpatentable over MacDonald and Harthoorn in further view of Hsu and van Leusen, and the rejection under 35 U.S.C. 103 of claims 25, 26, and 39-42 as being unpatentable over MacDonald and Harthoorn in further view of Langford, have been fully considered and are persuasive. Therefore, these rejections have been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Langford, previously cited as a secondary reference, in view of previously cited MacDonald.
Conclusion
No claims are allowed.
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Sef
/SUSAN E. FERNANDEZ/ Examiner, Art Unit 1651