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 .
Status of the Claims
Claims 1, 7-9, 11-14 and 17 are pending in the present application.
Information Disclosure Statement
The information disclosure statement submitted on 6 November 2025 was filed after the mailing date of the non-final Office action on 17 September 2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 1, 7-9 and 11-13 are rejected under 35 U.S.C. 103 as being unpatentable over Turke (US 2017/0360922 A1) in view of Arslanoglu et al. (The Journal of Maternal-Fetal and Neonatal Medicine, 2010), Kamarei (US 6,039,985) and Hudson et al. (Institute of Environmental Science & Research Limited, 2003).
Regarding instant claims 1 and 13, Turke teaches a nutritional supplement formulation including therapeutically effective amounts of a first allergen, a second allergen, a third allergen, and a pharmaceutically acceptable carrier, wherein the supplement may also contain a fourth, fifth, sixth, seventh and eighth allergen, and the allergens may be selected from the group consisting of a peanut allergen, a milk allergen, a wheat allergen, a tree nut allergen, an egg allergen, a soy allergen, a fish allergen, and a shellfish allergen ([0005], [0012],-[0033]; Claims 1-2). Turke teaches a method of preventing food allergies in a subject comprising administering therapeutically effective amounts of a first, second, and third allergen to the subject. Administration may be conducted orally. The subject may be from about 3 months to about 4 years old during the period of administration ([0007], [0039]-[0040], [0044]-[0045]; Examples 5-6; Claims 31-34, 39-40, 43-44). The term allergen includes a protein, including peanut proteins, tree nut proteins, milk proteins, what proteins, egg proteins, soy proteins, fish proteins, and shellfish proteins ([0008], [0014]-[0032]). The allergens may be administered as components of an infant formula, for example for bottle feeding or as a substitute or supplement for breastfeeding ([0044]).
Turke further teaches a baby formula comprising out of every 30 ounces of liquid formula, 100 micrograms of each of a peanut allergen, a tree nut allergen, a milk allergen, a wheat allergen, an egg allergen, a soy allergen, a fish allergen, and a shellfish allergen are included in the formula (Example 5). Turke also teaches a liquid solution containing a peanut allergen, a tree nut allergen, a milk allergen, a wheat allergen, an egg allergen, a soy allergen, a fish allergen, and a shellfish allergen in a pharmaceutical carrier, wherein each allergen is provided at a concentration of 50 micrograms per milliliter of the solution, and a child is administered five milliliters of solution (i.e., 250 micrograms of each allergen) every third day between the time he is three months old and the time is nine months old (Example 6).
Turke also teaches a method of preventing food allergies in a subject comprising administering therapeutically effective amounts of a first, second, and third allergen to the subject. Administration may be conducted orally. The subject may be from about 3 months to about 4 years old during the period of administration ([0007], [0039]-[0040], [0044]-[0045]; Examples 5-6; Claims 31-34, 39-40, 43-44). Turke further teaches that the subject may be from birth to 12 months old ([0010], [0045]; Example 5-6).
Turke does not explicitly disclose pasteurization at a temperature between 61.9 °C and 65 °C for at least 30 minutes.
Arslanoglu et al. teach that pasteurization at +62.5 °C for 30 min (Holder method) allows a good compromise between microbiological safety and nutritional and biological quality of the milk. In fact, this method destroys the pathogens in milk, including M. tuberculosis, and Bacillus cereus, as well as some viruses (HIV, HTVL 1-2, Cytomegalovirus, Herpes Simplex and Rubella). These results cannot be achieved constantly with the treatment at a temperature of 56 °C. The Holder method inactivates some biologically active, immunologic and anti-infective factors more than heat treatment at 56 °C: reduction of IgA, IgG, lysozyme, lactoferrin levels, specific IgA, and lactoferrin activities, lymphocytes, growth factors, cytokines, lipase, and lipase activity, and destruction of IgM and complement have been reported. However, with Holder pasteurization key nutritional factors (oligosaccharides, lactose, LCPUFA, fatty acids, gangliosides, protein sulfate and amino acids), and other biological factors (amylases, EGF) and A,D,E vitamins remain unchanged. Furthermore, Holder pasteurization maintains the bactericidal activity of the milk against E. coli better than high temperature short term pasteurization. It has also been shown that although Holder pasteurization decreases IgA concentration, the remaining molecules effectively inhibit bacterial (enteropathogenic E. coli) adhesion. Currently, Holder pasteurization is the most studied and recommended method for the heat treatment of donor human milk (pg. 12, Section 4.2.3).
Kamarei teaches infant formulas, wherein to ensure the destruction of all pathogenic microorganisms, it is necessary to heat the product to a given temperature and hold it at that temperature for a certain length of time before it is cooled again. The combination of temperature and holding time is very important as it determines the intensity of the heat treatment. The choice of time/temperature combination is a matter of optimization in which both microbiological effects and quality aspects must be taken into account. The original type of pasteurization was a batch process (also called Low Temperature Long Time, LTLT). The milk was heated to 63 °C in open vats and held at that temperature for 30 minutes.
Hudson et al. teach that heat treatments equivalent to pasteurization for common types of dairy produce include 63.0-65.8 °C for a minimum of 30 minutes (pg. 27). The FDA Grade “A” pasteurized milk ordinance define pasteurization as “..the process of heating every particle of milk or milk product, in properly designed and operated equipment, to one of the temperatures given in the following chart and held continuously at or above that temperature for at least the corresponding specified time (pg. 29):
Temperature
Time
63 °C (145 °F)
30 minutes
72 °C (161 °F)
15 seconds
89 °C (191 °F)
1.0 seconds
90 °C (194 °F)
0.5 seconds
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to pasteurize the infant formulations according to Turke to ensure the destruction of all pathogenic microorganisms, wherein a person of ordinary skill in the art would have been motivated to pasteurize the products within the temperature and minimum times conditions taught by Kamarei and Hudson et al. A person of ordinary skill in the art would have been able to determine the necessary temperature and time conditions for adequate pasteurization as reasonably taught by Kamarei and Hudson et al., including the Holder method of 63.0-65.8 °C for a minimum of 30 minutes.
Regarding the composition being in a ready to drink form, Turke teaches in some embodiments, all three allergens are made by dehydrating or freezing an allergenic precursor and grinding them down to a powder. In other embodiments, one or more allergens may be a purified protein, and one or more of the allergens may be a powder or oil of an allergenic substance ([0022]-[0032]). The allergens may be administered as components of an infant formula, for example for bottle feeding or as a substitute or supplement for breastfeeding ([0044]).
Regarding instant claims 7-9, Turke teaches a nutritional supplement formulation including therapeutically effective amounts of a first allergen, a second allergen, a third allergen, and a pharmaceutically acceptable carrier, wherein the supplement may also contain a fourth, fifth, sixth, seventh and eighth allergen, and the allergens may be selected from the group consisting of a peanut allergen, a milk allergen, a wheat allergen, a tree nut allergen, an egg allergen, a soy allergen, a fish allergen, and a shellfish allergen ([0005], [0012],-[0033]; Claims 1-2).
Regarding instant claim 11, Turke teaches that when the allergen is administered to the subject, the therapeutically effective amount of each antigen, on a per dose basis, may range from about 10 picograms to about 1 gram of allergen, or about 100 picograms to about 100 milligrams, or about 100 picograms to about 10 milligrams, or about 1 nanogram to about 1 milligram, or about 10 nanograms to about 500 micrograms, or about 100 nanograms to about 100 micrograms, or about 200 nanograms to about 50 micrograms, or about 500 nanograms to about 40 micrograms, or about 1 microgram to about 35 micrograms, or about 2 micrograms to about 30 micrograms, or about 5 micrograms to about 25 micrograms, or any amount in any of the disclosed ranges ([0050]).
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to determine the effective amount of each allergen based on the teachings of Turke. Turke teaches that the effective amount of each antigen, on a per dose basis, may be as much as about 1 gram of allergen, and the compositions may comprise from three to eight allergens, which would be a total of 3 to 8 grams of allergen per dose. Turke further teaches that as the skilled artisan will appreciate, lower or higher doses than those recited may be required. Specific dosage and treatment regimens for any particular subject will depend upon a variety of factors, including the activity of the specific antigen employed, the age, body weight, general health status, sex, diet, time of administration, rate of excretion, drug combination, and the patient’s disposition to the allergy in question and the judgement of the treating physician ([0052]). Therefore, a person of ordinary skill in the art would have been able to determine through routine experimentation, based on several factors, the optimum concentration of allergens within the range taught by Turke.
Regarding instant claim 12, as discussed above, Kamarei and Hudson et al. teach pasteurization of milk products by heating at 62-65 °C for a minimum of 30 minutes. As evidenced by the instant specification, pasteurization of milk protein according to the Holder pasteurization and HTST pasteurization methods yields a composition wherein at least 20% of said milk allergens are non-denatured. Therefore, pasteurizing the milk protein-containing composition according to Turke with the pasteurization method according to the Holder method taught by Kamarei and Hudson et al. would necessarily result in a composition wherein at least 20% of said milk allergens are non-denatured.
Response to Arguments
Applicant’s Remarks filed 16 January 2026 have been fully considered but they are not persuasive. Applicant argues, as explained in detail in the Declaration filed 31 March 2025, the skilled artisan reading Turke in combination with the other references would still use HTST pasteurisation to pasteurize the composition, and in doing so would not have arrived at the presently claimed composition or process. Applicant asserts that they have demonstrated that pasteurisation of milk at a temperature between 61.9°C and 65°C for at least 30 minutes produces a drinkable infant composition in a ready to drink form that unexpectedly retains a greater degree of allergenicity - at least 3-10 folds - compared to pasteurisation at a temperature 72°C for 15 seconds or at 70°C for 3 or 20 minutes. This temperature range is effective in destroying contaminants while minimizing the denaturation of allergenic proteins present in milk and egg. Therefore, the currently claimed inventions provide a significantly improved process for sterilizing an allergenic composition while advantageously retaining a high degree of allergenicity post-sterilization.
Applicant argues that none of the references, including Turke, Arslanoglu, Kamarei, Hudson and Kent, alone or in combination, discloses or suggests pasteurisation of a composition in a ready to drink form, e.g., milk, at a temperature between 61.9°C and 65°C for at least 30 minutes would retain a greater degree of allergenicity or maintains a lower degree of denaturation of beta lactoglobulin (an allergenic milk protein) and ovalbumin (an allergenic egg protein), as compared to HTST pasteurization methods taught by, for example, Kamarei or Hudson.
Applicant argues that Arslanoglu relates to the guidelines for the establishment and operation of a donor human milk bank. In contrast, the claimed inventions relate to a drinkable infant composition, examples of which include infant supplements and infant formulas. Turke also relates to a nutritional supplement formulation for infants. Therefore, the skilled person would not look to Arslanoglu when looking to provide a pasteurized drinkable infant composition that unexpectedly retains a greater degree of allergenicity. Applicant argues that Arslanoglu acknowledges that the Holder method inactivates some biologically active, immunologic and anti-infective factors more than heat treatment at 56°C. This teaching is important because as explained in the present application, milk and egg possess immunogenic potential (Example 5). Crucially, this immunogenic potential is provided by the native (not denatured) proteins present in milk and egg, and it is this immunogenic potential that translates into the allergenic profile of milk and egg. Thus, upon reading Arslanoglu, the skilled person would be explicitly taught that the Holder pasteurization method would reduce the immunogenic potential of a composition.
Applicant also argues that Bertino explicitly states that the Holder pasteurization method would inactivate immunological factors. Thus, upon reading Bertino, the skilled person would be explicitly taught that the Holder pasteurization method would reduce the immunogenic potential of a composition.
Applicant further argues that from reading Roth-Walter as a whole, it seems that pasteurized and therefore aggregated ALA and BLG cause sensitization, but only native ALA and BLG cause an allergic response (anaphylaxis is disclosed) when ingested.
The examiner respectfully argues that Arslanoglu et al. teach that pasteurization at +62.5 °C for 30 min (Holder method) allows a good compromise between microbiological safety and nutritional and biological quality of the milk. In fact, this method destroys the pathogens in milk, including M. tuberculosis, and Bacillus cereus, as well as some viruses (HIV, HTVL 1-2, Cytomegalovirus, Herpes Simplex and Rubella). These results cannot be achieved constantly with the treatment at a temperature of 56 °C. The Holder method inactivates some biologically active, immunologic and anti-infective factors more than heat treatment at 56 °C: reduction of IgA, IgG, lysozyme, lactoferrin levels, specific IgA, and lactoferrin activities, lymphocytes, growth factors, cytokines, lipase, and lipase activity, and destruction of IgM and complement have been reported. However, with Holder pasteurization key nutritional factors (oligosaccharides, lactose, LCPUFA, fatty acids, gangliosides, protein sulfate and amino acids), and other biological factors (amylases, EGF) and A,D,E vitamins remain unchanged. Furthermore, Holder pasteurization maintains the bactericidal activity of the milk against E. coli better than high temperature short term pasteurization. It has also been shown that although Holder pasteurization decreases IgA concentration, the remaining molecules effectively inhibit bacterial (enteropathogenic E. coli) adhesion. Currently, Holder pasteurization is the most studied and recommended method for the heat treatment of donor human milk (pg. 12, Section 4.2.3).
Also, Roth-Walter et al. (Allergy, 2008) teach that casein is generally considered the major allergen in milk-allergic patients, followed by the whey proteins BLG and ALA, since antibodies to casein, but not consistently to ALA and BLG are readily detected in nearly all milk allergic individuals (pg. 888, col. 1). Increased allergenicity in milk-allergic mice challenged with homogenized and pasteurized milk compared with untreated bovine milk has already been observed and associated with the homogenization procedure. However, our findings indicate that a higher degree of sensitization is due to pasteurization/aggregation of the whey proteins and enhanced uptake by Peyer’s patches. It is to note that, so far, all known major food allergens tend to form pseudo-lipophilic protein-bodies, micelles or aggregates and consequently their ability to enter the body through absorptive intestinal epithelial cells is predicted to be diminished. In pasteurized milk, CAS and aggregated whey proteins might set the stage for an anaphylactic response but it may be the soluble whey proteins, still present in pasteurized milk, that actually result in the allergic event. In conclusion, our results suggest that pasteurization leads to aggregation of whey proteins but not CAS. The formation of aggregates changes the path of antigen uptake, away from absorptive enterocytes to Peyer’s patches. As a consequence, pasteurized BLG leads to enhanced IgE as well as Th2 cytokine responses in the initial sensitization step, suggesting that the formation of aggregates is one important feature of food allergens. In contrast, only soluble milk proteins trigger anaphylaxis readily, since transepithelial uptake across the small intestinal epithelium is not impaired. Since milk proteins are usually consumed in a pasteurized form, this may be clinically relevant. These findings support the hypothesis that food processing may contribute to the increasing prevalence of sensitization to food proteins in westernized countries (pg. 888, col. 2).
A person of ordinary skill in the art would have been motivated to pasteurize the formulations of Turke by the Holder method at 62.5 °C for 30 min in order to sanitize the composition while maintaining key nutritional factors and other biological factors. Also, as discussed above, as evidenced by Bertino et al. and Roth-Walter et al., a person of ordinary skill in the art would reasonably expect the Holder method of pasteurization to maintain the sensitization effect of the formulation.
Regarding the data in Example 4 of the specification. Table 2 indicates that raw milk unprocessed had 0.0% residual BLG/initial BLG, and that high heat treated milk at 80 °C for 20 min led to the highest residual allergenicity, while UHT at 145 °C for 5 sec led to higher percentage of residual BLG/initial BLG compared to 63 °C/30 min and 72 °C/15 sec. However, Example 3 states that high-heat, high-time treatments (80, 90 °C/20 min) and UHT treatments (145 °C/5 sec) led to the highest levels of whey protein denaturation. Applicant argued in their Remarks filed 24 July 2024 and 6 January 2025 that “if denaturation is lower, allergenicity is greater”. Therefore, it is confusing that denaturation was greatest for 80, 90 °C/20 min and 145 °C/5 sec, while also yielding the highest levels of allergenicity, which appears to contradict the argument that if denaturation is lower, allergenicity is greater. Also, it is confusing that raw unprocessed milk had 0.0% residual BLG/initial BLG resulting in no allergenicity. One would expect the raw milk to possess allergenicity compared to the heat treated milk.
Claims 14 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Turke (US 2017/0360922 A1) in view of Arslanoglu et al. (The Journal of Maternal-Fetal and Neonatal Medicine, 2010), Kamarei (US 6,039,985) and Hudson et al. (Institute of Environmental Science & Research Limited, 2003) as applied to claims 1, 7-9 and 11-13 above, further in view of Kent et al. (Nutrients, 2015).
The teachings of Turke, Arslanoglu et al., Kamarei and Hudson et al. are discussed above.
Regarding instant claims 14 and 17, Turke, Arslanoglu et al., Kamarei and Hudson et al. do not explicitly disclose the steps of blending the allergens, homogenizing the mixture, and pasteurizing said mixture, as instantly claimed.
Kent et al. teach a wet-mix process for producing powdered infant formula (PIF) involves blending, homogenising and pasteurizing all the components together. Due to the inclusion of a heat-treatment step the microbiological quality of the finished product is far less reliant on the base ingredients. This process also ensures the uniform distribution of nutrients throughout each batch (pg. 1221, para. 1).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the instant claims to prepare the compositions according to Turke by blending, homogenizing, and pasteurizing the components as reasonably taught by Kent et al. It would have been obvious to pasteurize the compositions within the temperature/time ranges taught by Kamarei and Hudson et al., as discussed above.
Response to Arguments
Applicant argues that Kent fails to remedy the above deficiencies. Therefore, the examiner’s response above is repeated here as well.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nathan W Schlientz whose telephone number is (571)272-9924. The examiner can normally be reached 10:00 AM to 6:00 PM, Monday through Friday.
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/N.W.S/Examiner, Art Unit 1616
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616
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