DETAILED ACTION
The present application is a national stage entry of PCT/EP2021/085819, filed 15 December 2021, which claims foreign priority to EP20214739.3, filed 16 December 2020.
The preliminary amendment filed 02 June 2023 is acknowledged. Claims 1-20 are pending in the current application. Claim 15 is withdrawn as being drawn to a non-elected invention. Claims 1-14 and 16-20 are examined on the merits herein.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-14 and 16-20 in the reply filed on 26 September 2025 is acknowledged.
Claim 15 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 26 September 2025.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 8 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 8 recites the limitation “and optionally of DSLNT” in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 8 depends from claim 1, which does not positively recite “DSLNT”.
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.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], 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 8 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, 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.
Claim 8 recites the limitation “and optionally of DSLNT” in line 3. However, this limitation is not recited in claim 1, from which it depends. 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
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 1-14, 16, 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Thomas et al. (US Patent Application Publication No. 2015/0064220, cited in IDS submitted 02 October 2025) in view of Kulinich et al. (Carbohydrate Research, 2016, vol. 432, pp. 62-70, cited in PTO-892).
Thomas et al. teach a method of enhancing cell-mediated immunity in an individual in need thereof, the method comprising administering to the individual in need thereof a nutritional composition comprising at least one of a sialylated human milk oligosaccharide (HMO) and a fucosylated HMO (claim 1). The individual in need includes infants, pediatrics and adults (claim 2). The nutritional composition is a liquid comprising from about 0.001 mg/mL to about 20 mg/mL of either the sialylated or fucosylated HMO (claim 3). Alternatively, the composition is a powder comprising from about 0.0005% to about 5% of either the sialylated or fucosylated HMO (claim 4). The sialylated HMO includes lactosialotetraose (i.e. sialyllacto-N-tetraose, LST), (claim 5). The fucosylated HMO includes lacto-N-fucopentaose (claim 7). The composition enhances T-cell mediated responses including T-cell regulatory responses (claims 13 and 14). The composition may further comprise additional ingredients including prebiotics and probiotics (para [0090]). The composition further comprises fat and protein (para [0075]). And it can be formulated as an infant formula or adult formula (para [0076]). Various sources of fat including vegetable fat and milk fat are described in paragraphs [0083], [0084] and [0133], see e.g. example 1 with condensed skim milk (i.e. bovine milk fat). Thomas et al. expressly teach obtaining bovine-based protein (para [0086]). The ratio of sialylated and fucosylated HMOs are varied to dampen a chronic inflammatory condition without inducing global immunosuppression or enhance a suppressed immune condition without inducing inflammation (para [0014]). Example 6 comprises 0.0948 kg HMO mix per 1000 kg of product (0.01 wt.%). The HMO mix comprises 21.4% fucosylated HMO (8.9% LNFP, 6.7% MFLNH and 5.8% 2’FL) and 14.3% sialylated HMO (11.1% LST, 2.1% 6’SL and 1.1% 3’SL).
Thomas et al. do not expressly disclose LSTa (present claim 1).
Kulinich et al. teach sialo-containing HMOs include 3’-SL, 6’-SL, DSLNT, LST a, LST b, and LST c (figure 3). Kulinich et al. teach fucosylated and sialylated HMOs block pathogenic bacteria from binding to intestinal epithelium (p.64, last para). LST a, LST b and LST c comprise the same four monosaccharide units: N-acetylglucosamine, galactose, glucose and sialic acid; and via the same α/β anomeric configurations, linked to each other in different arrangements (i.e. structural isomers), (see fig. 3). Kulinich et al. teach sialylated HMOs are known to effect immunity, including mediating Th2 response (p.65). They are also known to down-regulate inflammation. Of the fucosylated HMOs, LNFP III was shown to significantly promote Th2 response in vivo and in vitro (p.63-64, bridging para). LNFP III was also shown to activate NK cells, which are responsible for lysis of malignant and virus-infected cells.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a formulation of LNFP III with LSTa, according to the teachings of Thomas et al.
From Thomas et al., the ordinary artisan would have known formulations comprising at least one fucosylated HMO combined with at least one sialylated HMO are useful for enhancing cell-mediated immunity, including T-cell mediated response. According to Thomas et al., suitable fucosylated HMOs at least include LNFP, MFLNH and 2’FL. Suitable sialylated HMOs at least include LST, 6’SL and 3’SL.
The ordinary artisan would have been motivated to combine LNFP III with LSTa, because LNFP III was shown to significantly promote Th2 response in vivo and in vitro. LSTa is one of three forms of LST, wherein Thomas et al. and Kulinich et al. teach sialylated HMOs including LST are known to effect immunity, including mediating Th2 response. Since LSTa is one of three forms of LST, one having ordinary skill in the art would have had a reasonable expectation of success in using it according to Thomas et al.
See MPEP 2144.09(I), “A prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities.”.
The recitation “wherein the synthetic composition is effective as an anti-inflammatory agent and/or has an effect of one or more of: upregulating FoxP3…” in claim 14 is an intended use of the composition.
With respect to the claimed weight ratio, one having ordinary skill in the art would have been motivated to formulate LNFP III and LSTa at a 1.5:1 weight ratio because Thomas et al. teach using an HMO mix comprising 21.4% fucosylated HMO (8.9% LNFP, 6.7% MFLNH and 5.8% 2’FL) and 14.3% sialylated HMO (11.1% LST, 2.1% 6’SL and 1.1% 3’SL).
The amount of LST and LNFP taught by Thomas et al. lies within the claimed ranges.
With respect to using milk fat from bovine milk, Thomas et al. teach an exemplary composition comprising condensed milk. While Thomas et al. do not expressly disclose the condensed milk is from cows, one having ordinary skill in the art would have been motivated to use milk fat from bovine milk because Thomas et al. expressly teach using protein from bovine is preferable.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Claim(s) 5-7, 17 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Thomas et al. and Kulinich et al. as applied to claims 1-14, 16, 19 and 20 above, and further in view of Nauta et al. (WO 2011/096808 A1, cited in PTO-892).
Thomas et al. teach as discussed above.
Thomas et al. do not expressly disclose DSLNT (present claims 5-7, 17 and 18).
Nauta et al. teach a dietetic, nutritional, nutraceutical or pharmaceutical composition, comprising at least one sialyloligosaccharide; and living Bacteroides ssp (i.e. a probiotic, claim 1). The composition is intended to increase the relative abundance of beneficial microorganisms (abstract). These microorganisms produce short chain fatty acids (SCFA), which modulate the immune system (p.2:4-10). The one or more sialyloligosaccharide is selected from the group consisting of disialyllacto-N-tetraose (DSLNT), and sialyllacto-N-tetraose a (LSTa), etc. (claim 3). The composition comprises the at least one sialyloligosaccharide in an amount of 0.005-20 g per unit dose, preferably 0.01-10 g per unit dose (claim 5). Table 3 comprises 0.2 g sialyllactose (another HMO) per 12 g of the composition (formula B, or formula C not including the weight of the probiotics), so that the composition comprises 1.6 wt.% sialyloligosaccharide of the total dry weight of the composition. Table 3 also lists fats, protein and carbohydrates. Fats include corn oil (i.e. vegetable fat; p.12:26-29). The composition is formulated as an infant formula (claim 6), and as a complete food product (p.7:5-8). The composition further comprises a prebiotic (claim 9). The composition further comprises milk fat (claim 10). The composition may further comprise a fucosylated oligosaccharide (claim 9). The composition is formulated to be administered to a human being between 0 and 6 years, preferably between 0 and 6 months (claim 18).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine DSLNT with LSTa and LNFP III.
According to MPEP 2144.06: “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Combining known therapies into a single therapy is a commonly applied method for identifying improved therapeutic outcomes with minimal adverse effect for the patient because each monotherapy is already known to be effective. Here, LNFP and LST (includes LSTa, LSTb and LSTc) are known to effect immunity, including mediating Th2 response, while DSLNT and LST modulate the immune system by increasing of the abundance of beneficial bacteria. Thus, the skilled artisan would have been motivated to combine the three human milk oligosaccharides wherein they each produce different effects for modulating the immune system.
The ordinary artisan would have looked to the teaching of Thomas et al. and Nauta et al. for determining the amount of each oligosaccharide. Nauta et al. teach using similar amounts of each sialylated oligosaccharide. With respect to the claimed weight ratio, one having ordinary skill in the art would have been motivated to formulate LNFP III and LSTa at a 1.5:1 weight ratio because Thomas et al. teach using an HMO mix comprising 21.4% fucosylated HMO (8.9% LNFP, 6.7% MFLNH and 5.8% 2’FL) and 14.3% sialylated HMO (11.1% LST, 2.1% 6’SL and 1.1% 3’SL). Using similar amounts of sialylated HMO would suggest a 1.5:1:1 weight ratio of LNFPIII:LSTa:DSLNT.
The ordinary artisan would have been motivated to optimize the amounts given that Thomas et al. teach the ratio of sialylated and fucosylated HMOs are varied to dampen a chronic inflammatory condition without inducing global immunosuppression or enhance a suppressed immune condition without inducing inflammation. The percent by weight of sialylated and fucosylated HMOs lie within the claimed ranges, including claim 18.
See MPEP 2144.05(II), “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.”.
Thus, the claimed invention as a whole is prima facie obvious over the combined teaching of the prior art.
Conclusion
In view of the rejections to the pending claims set forth above, no claim is allowed.
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/BAHAR CRAIGO/
Primary Examiner
Art Unit 1699