DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
CONTINUING DATA
This application is a 371 of PCT/EP2019/084308 12/10/2019
FOREIGN APPLICATIONS
EP 18212616.9 12/14/2018
A request for continued examination under 37 CFR 1.114 was filed in this application after appeal to the Patent Trial and Appeal Board, but prior to a decision on the appeal. 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examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on November 26, 2025 has been entered.
Claims 1-7, 10-13, 16-17, 19-20, and 22-25 are pending.
Applicant’s election without traverse of Group II in the reply filed on May 17, 2024 is acknowledged.
Claims 1-7, 10, and 13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on May 17, 2024.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
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.
Claims 11-12, 16-17, 19-20, and 22-25 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. The claims were amended to require that the aqueous composition is stable against hydrolysis, degradation and/or isomerization of the at least one oligosaccharide at 37°C for at least 60 days. The specification does not provide literal support for this limitation, and “stable” is not defined in the specification. The subject matter of the claim need not be described literally, but if a claim is amended to include an addition of a limitation to the disclosure as filed, the claimed subject matter is not described in that application. MPEP 2163.02. The claims require that the composition is stable “for at least 60 days” or longer in claims 23-25, which has no upper limit, and is an addition of a limitation to the disclosure as filed. Applicant indicated that the new limitation finds support in Figures 1, 2A, and 2D.
In Figure 1, LNnT fructose isomer and 2FL fructose isomer increased over time at pH 6 and 37°C. Lactose remained fairly constant, which some small increases and decreases over time. Lacto-N-triose increased slowly over time. Thus, at pH 6, some degradation is occurring over time. Because “stable” is not defined, it is unclear whether Figure 1 is illustrative of a stable composition or not.
In Figure 2A, the concentration of 2FL at pH 6 remained higher than at pH 7 over time. The concentration did decrease somewhat during the first 3 months, then increased again at 6 months and then remained relatively constant after 6 months up to 14 months. Again, it is unclear whether Figure 2A is illustrative of a stable composition or not.
In Figure 2D, the concentration of LNnT at pH 6 went up and down throughout the first 14 months. At 3 months, the concentration at pH 6 was higher than at pH 7, but at 6 months, the concentration at pH 7 was higher than at pH 6. Again, it is unclear whether Figure 2D is illustrative of a stable composition or not.
“Stable” is not defined in the specification, and is a relative term. It is not clear what is required for the composition to meet the limitation “stable.” It is impossible to determine whether the examples in Figures 2A and 2D were “stable” because stability is not defined and the concentrations of HMOs in those examples were not constant.
Compositions which are stable for at least 60 days are not disclosed because data for 3’-SL, 6’-SL, DFL, LNT, and 3-FL is not provided at all and the data for 2FL and LNnT is unclear regarding stability. Data is not provided after about 14 months, so compositions which are stable for “at least” a period of time with no upper limit are not disclosed. To summarize, support is not provided over the entire claimed range of HMOs, “stable” is not defined and cannot be discerned (so it cannot be considered to be disclosed), and the claims include a time period with no upper limit.
Claim 23 requires that the oligosaccharides consist of 2’FL and LNnT, and 2’FL and LNnT are the only oligosaccharides in the composition. Applicant indicated that support could be found in paragraphs starting at [0150]. Paragraph [0150] does disclose such a composition, which was used for stability testing. Claim 23, however, is a method of treatment. The specification does not disclose a method of treatment using an oligosaccharide mixture consisting of 2’FL and LNnT in the absence of other oligosaccharides.
This is a new matter rejection.
Claims 11-13, 16-17, 19-20, and 22-25 are 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.
The claims require that the composition is stable for at least 60 days, or longer in claims 23-25. The specification does not define “stable.” The term “stable” in the claims is a relative term which renders the claim indefinite. The term “stable” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Figures 2A and 2D do not show a composition wherein the concentration of HMO is constant over time, so “stable” apparently does not mean constant. Figure 2D shows a composition wherein the HMO concentration is higher at pH 6 at certain times points and lower in others, so “stable” does not necessarily mean compared to pH 7. Thus, the specification does not provide a standard for ascertaining the requisite degree of stability.
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.
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.
Claim(s) 11-12, 16-17, 19-20, and 22-25 are rejected under 35 U.S.C. 103 as being unpatentable over Davis (WO 2013/032674 A1, of record).
Davis teaches that administration of human milk oligosaccharides is beneficial to the gastrointestinal tract of preterm infants. See abstract. HMOs are described as immune enhancing [0051] and prebiotic [0057]. The composition contains HMOs and is a liquid human milk fortifier for preterm infants [0068]. Treatment of low birth weight infants is also taught [0049]. The HMOs include at least one of 3’-SL, 6’-SL, 2’-FL, 3’-FL, and LNnT (claim 3). The HMOs enhance expression of proteins such as TFF3, MUC2, and RELM to aid in cell healing, resolution of inflammation, and promotion of barrier function. The HMOs also enhance the production of isobutyrate in the colon, which would be helpful for preterm infants [0010]. The impact of HMOs is dose-dependent, with the higher concentration resulting in more pronounced increases in expression of MUC2 and TFF3 [0125]. The composition has a pH from 5.5 to 7.3 or 6.2 to 7.2 [0046]. Davis teaches that, for a concentrated nutritional liquid, the concentration of HMOs is up to about 4% [0056] and the concentration of total carbohydrates is up to about 10-75% or 10-50% or 15-37% [0069].
Davis does not teach an example having a pH in the claimed range and does not teach a concentration of the claimed oligosaccharides ranging from 5 to 50% w/w.
It would have been obvious to one ordinary skill in the art at the time the application was filed to administer an infant formula or fortifier containing HMOs and at a pH of 5.5 to 6.5 or 5.8 to 6.3. MPEP 2144.05 states that where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists. In this instance, the claimed ranges lie inside the prior art range 5.5 to 7.3 and overlap with the prior art range 6.2 to 7.2.
It would have been obvious to one of ordinary skill in the art at the time the application was filed to prepare concentrated nutritional liquids having oligosaccharides having glucose at the reducing end at a concentration of 5-50%, 8-35% or 10-30%.
The skilled artisan would optimize the concentration of the HMOs using routine experimentation to arrive at a suitable milk fortifier using the guidance provided by Davis. Davis teaches the purpose of the HMOs and the mechanisms by which the HMOs support intestinal health, so the concentration of HMOs is a result-effective variable. Davis explicitly teaches that the results of administration of HMOs are dose-dependent, with the higher concentration providing greater results, so the skilled artisan would have been motivated to prepare compositions with a greater concentration of HMOs. 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. MPEP 2144.05.
It would have been obvious to administer the composition wherein the HMOs consisted of 2’FL and LNnT and no other oligosaccharides are present because Davis teaches that the composition contains one or more of a list of only 6 oligosaccharides comprising 2’FL and LNnT. 2’FL is mentioned alone in claim 4. Davis teaches that any product form can be used, which allows for oral delivery of the HMOs [0038]. A combination of two can be used [0050]. The compositions may consist of the essential elements of the composition [0037]. Oligosaccharides in addition to HMOs are optional [0057].
The “wherein” limitation regarding stability which was added at the end of claim 11 is considered to be an inherent property of the composition at the pH suggested by Davis because the current specification states that stabilization against isomerization, degradation, and hydrolysis is a function of pH. Paragraphs [0015], [0152].
Claim(s) 11-12, 16-17, 19-20, and 22-25 is/are rejected under 35 U.S.C. 103 as being unpatentable over Davis (WO 2013/032674 A1) in view of Sprenger (US 8,591,981 B2, 2013, previously cited by the examiner).
Davis teaches that administration of human milk oligosaccharides is beneficial to the gastrointestinal tract of preterm infants. See abstract. HMOs are described as immune enhancing [0051] and prebiotic [0057]. The composition contains HMOs and is a liquid human milk fortifier for preterm infants [0068]. Treatment of low birth weight infants is also taught [0049]. The HMOs include 3’-SL, 6’-SL, 2’-FL, 3’-FL, and LNnT (claim 3). The composition has a pH from 5.5 to 7.3 or 6.2 to 7.2 [0046]. The HMOs enhance expression of proteins such as TFF3, MUC2, and RELM to aid in cell healing, resolution of inflammation, and promotion of barrier function. The HMOs also enhance the production of isobutyrate in the colon, which would be helpful for preterm infants [0010]. The impact of HMOs is dose-dependent, with the higher concentration resulting in more pronounced increases in expression of MUC2 and TFF3 [0125]. The composition has a pH from 5.5 to 7.3 or 6.2 to 7.2 [0046]. Davis teaches that, for a concentrated nutritional liquid, the concentration of HMOs is up to about 4% [0056] and the concentration of total carbohydrates is up to about 10-75% or 10-50% or 15-37% [0069].
Davis does not teach an example having a pH in the claimed range and does not teach the concentration 5-50%.
Sprenger teaches oligosaccharide mixtures. See abstract. A pH in the range of 3-7.5 or 5 to 6 is preferred to prevent oligosaccharide hydrolysis, including desialylation of sialyllactose. Column 5, first paragraph. In one example, the pH was 6 to 6.5. See example 2.
It would have been obvious to one ordinary skill in the art at the time the application was filed to administer an infant formula or fortifier containing HMOs and at a pH of 5.5 to 6.5 or 5.8 to 6.3. MPEP 2144.05 states that where the claimed ranges overlap or lie inside ranges disclosed by the prior art, a prima facie case of obviousness exists. In this instance, the claimed ranges lie inside the prior art range 5.5 to 7.3 and overlap with the prior art range 6.2 to 7.2. Additionally, Sprenger teaches that oligosaccharide hydrolysis is prevented in the pH range of 5 to 6 or 6 to 6.5. The skilled artisan would have prepared an infant formula or fortifier at the claimed pH because the conditions are taught generally by Davis and a pH of around 5-6 or 6-6.5 would have been further preferred because it would improve the stability of oligosaccharides.
The skilled artisan would optimize the concentration of the HMOs using routine experimentation to arrive at a suitable milk fortifier using the guidance provided by Davis. Davis teaches the purpose of the HMOs and the mechanisms by which the HMOs support intestinal health, so the concentration of HMOs is a result-effective variable. Davis explicitly teaches that the results of administration of HMOs are dose-dependent, with the higher concentration providing greater results, so the skilled artisan would have been motivated to prepare compositions with a greater concentration of HMOs. 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. MPEP 2144.05.
It would have been obvious to administer the composition wherein the HMOs consisted of 2’FL and LNnT because Davis teaches that the composition contains one or more of a list of only 6 oligosaccharides comprising 2’FL and LNnT. 2’FL is mentioned alone in claim 4. Davis teaches that any product form can be used, which allows for oral delivery of the HMOs [0038]. A combination of two can be used [0050]. The compositions may consist of the essential elements of the composition [0037]. Oligosaccharides in addition to HMOs are optional [0057].
The “wherein” limitation regarding stability which was added at the end of claim 11 is considered to be an inherent property of the composition at the pH suggested by Davis because the current specification states that stabilization against isomerization, degradation, and hydrolysis is a function of pH. Paragraphs [0015], [0152].
Response to Arguments
Applicant argues that Davis does not disclose the new limitation regarding stability. This argument is not persuasive because the stability of the composition is an inherent property. The “wherein” limitation regarding stability which was added at the end of claim 11 is considered to be an inherent property of the composition at the pH suggested by Davis because the current specification states that stabilization against isomerization, degradation, and hydrolysis is a function of pH. Paragraphs [0015], [0152].
Applicant argues that the office is cherry picking figures 1A-1D in Davis because Figure 1E shows a reduction in the highest dose. This argument is not persuasive because Figures 1A-1D all show a dose dependent effect for MUC2, TFF3, RELMB, and CHST5. These results are not negated by Figure 1E, which is directed to GAL3ST2. Davis teaches that Figures 1A-1E depict the dose dependency on expression of several genes involved in the healing response of the gastrointestinal tract. The skilled artisan would have increased the concentration in order to obtain increased results regarding MUC2, TFF3, RELMB, and CHST5.
Applicant argues that Davis’s samples are not aimed at being stored, so Davis does not suggest the claimed stability at 37°C. This argument is not persuasive because stability is an inherent property of Davis’s compositions due to the pH.
Applicant argues that oligosaccharides often cannot be concentrated sufficiently in aqueous solution, so heat treatment is used, resulting in isomerization. Davis does teach a heat sterilization step [0017], which is done on either a diluted solution or a powder [0102]. Davis suggests a pH which the current specification states protects against isomerization.
Applicant argues that the skilled artisan would not have prepared the composition wherein 2’FL and LNnT are the only oligosaccharides in the composition because Sprenger is directed to a mixture derived from animal milk and Davis does not provide any reason either. This argument is not persuasive because Davis teaches that the composition can comprise one or more HMOs, that the composition can consist of its essential elements, and that additional oligosaccharides are optional. The rejection is not based on Sprenger alone.
For all these reasons, the rejections are maintained.
Conclusion
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/LAYLA D BERRY/ Primary Examiner, Art Unit 1693