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 .
Response to Amendment/Status of Claims
Receipt of Arguments/Remarks filed on 02/27/2026 and the supplemental amendment filed 04/16/2026 is acknowledged. Claims 8-9,11-14 and 16 were/stand cancelled. Claims 1-7 were amended. Claims 17-22 are new.
Applicant elected Group I (claims 1-7 and 14) without traverse in the reply filed on 10/01/2025. Claims 10 and 15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 10/01/2025.
Applicant elected species miR-3126 without traverse and the Examiner expanded the species of miRs to include those species taught in the prior art.
Claims 1-7 and 17-22 are under examination.
Priority
This application is a 371 of PCT/EP2021/068783, filed 07/07/2021, which claims benefit to EP20185312.4, filed 07/10/2020, according to the filing receipt dated 05/04/2023.
Withdrawn Objections and Rejections
Applicant’s arguments and amendments, see page 6, filed 02/27/2026, with respect to the objection to the specification regarding the sequence requirements have been fully considered and are persuasive due to the amendment to the specification providing sequence identifiers for the nucleotide sequences and correcting the identification of the Tables. The objection to the specification has been withdrawn for these issues but the objection to the specification remains as there is still browser executable code in the specification. See below.
Applicant’s arguments and amendments, see page 6, filed 02/27/2026, with respect to the objection to claim 7 have been fully considered and are persuasive due to the amendment to claim 7 adding “further”. The objection to claim 7 has been withdrawn.
Applicant’s arguments and amendments, see pages 7-8, filed 02/27/2026, with respect to the rejection(s) of claim(s) 1-3 and 14 under 35 U.S.C. 102(a)(1) as anticipated by Basu et al. and claims 4-7 under 35 U.S.C. 103 as unpatentable over have been fully considered and are persuasive due to the amendment to claim 1 adding at least one non-digestible oligosaccharide. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of the amendment to claim 1 requiring at least one non-digestible oligosaccharide and that the nutritional composition is not natural human or animal milk.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See page 13, reciting http://www.mirbase.org/.
Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-7 and 17-22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature without significantly more, as described in MPEP 2106.04(b)(II).
Regarding Step 1 of the Eligibility Analysis for 35 USC 101, claims 1-7 and 17-22 recite “a nutritional composition”, and are therefore directed to a product, which is one of the statutory categories of invention.
Regarding Step 2A Prong One of the Eligibility Analysis, claims 1-7 and 17-22 recite at least one judicial exception that is a product of nature, which is miR-3141, as well as at least one non-digestible oligosaccharide which is a product of nature, and claims 5-7 recite additional miRNA products of nature. The instant specification discloses that “a nutritional composition” means a composition that nourishes a subject, and does not include natural milk of human or animal origin (page 4, lines 16-19). miR-3141, miR-3126, miR-3184 as well as many of the miRs recited in claim 5 are products of nature as shown by Basu et al. (US20130330364, Published 12 Dec 2013). Basu et al. teach a formulation containing secreted products that are part of a vesicle derived from renal cells, including secreted vesicles, and the secreted vesicles comprise microRNAs, preferably human miRNA, and one or more miRNAs are selected from the group consisting of…miR-3141… let-7b, let-7c…miR-19b…miR-22…miR24-1…miR-25…miR-29a..miR30a…miR-92a..miR-99a…miR-100...miR-197…miR-30d…miR-181a-1...miR-181b-1…miR-205…miR-210…miR-221…miR-125b-2…miR-125a…miR-149…miR-193a…miR-320a…miR-200a…miR-99b…miR-130b…miR-30e…miR-375…miR378…miR-151…miR-425..miR-484…miR-146b…miR-574…miR-652…miR-320c…miR-3184…let-7d… miR-196a…miR-187..miR-516a…miR-92b… miR-3126 (paragraphs 0160-0161, pages 15-16). Therefore, Basu et al. teach these recited miRNAs are products of nature.
In addition, the recited non-digestible oligosaccharide is also a product of nature obtained from natural sources. The further ingredients in claim 22 (protein source, carbohydrate source, lipid source, vitamins and minerals) are also products of nature obtained from natural sources.
Per MPEP 2106.04(c), Where the claim is to a nature-based product produced by combining multiple components (e.g., a claim to "a probiotic composition comprising a mixture of Lactobacillus and milk"), the markedly different characteristics analysis should be applied to the resultant nature-based combination, rather than its component parts. For instance, for the probiotic composition example, the mixture of Lactobacillus and milk should be analyzed for markedly different characteristics, rather than the Lactobacillus separately and the milk separately. The markedly different characteristics analysis compares the nature-based product limitation to its naturally occurring counterpart in its natural state. Markedly different characteristics can be expressed as the product’s structure, function, and/or other properties, and are evaluated based on what is recited in the claim on a case-by-case basis. If the analysis indicates that a nature-based product limitation does not exhibit markedly different characteristics, then that limitation is a product of nature exception. Because the markedly different characteristics analysis compares the nature-based product limitation to its naturally occurring counterpart in its natural state, the first step in the analysis is to select the appropriate counterpart(s) to the nature-based product. When the nature-based product is derived from a naturally occurring thing, then the naturally occurring thing is the counterpart.
In the instant case, naturally occurring miRNA-3141, as well as the other recited miRNAs are the counterpart, and naturally occurring non-digestible oligosaccharides are the counterpart for the recited non-digestible oligosaccharide. MPEP 2106.04(c ) II. C. states, The final step in the markedly different characteristics analysis is to compare the characteristics of the claimed nature-based product to its naturally occurring counterpart in its natural state, in order to determine whether the characteristics of the claimed product are markedly different. The courts have emphasized that to show a marked difference, a characteristic must be changed as compared to nature, and cannot be an inherent or innate characteristic of the naturally occurring counterpart or an incidental change in a characteristic of the naturally occurring counterpart. Myriad, 569 U.S. at 580, 106 USPQ2d at 1974-75. Thus, in order to be markedly different, the inventor must have caused the claimed product to possess at least one characteristic that is different from that of the counterpart”.
Claims 1-7 and 17-22 do not recite any markedly different characteristics of the recited miRNAs from these miR’s found in nature as there are no modifications recited in the compound or any other properties recited. As miR-3141 and the other above miR’s are expressed in humans, the claims encompass any human tissue, cell or body fluid. In addition, no characteristics of the non-digestible oligosaccharide, or the protein source, carbohydrate source, lipid source, vitamins and minerals in claim 22 are recited in the claims to result in markedly different characteristics from that found in nature. The entire composition does not recite any characteristics to result in a characteristic different from that found in nature.
Next then, Step 2A Prong Two is analyzed to determine if the claim recites additional elements that integrate the judicial exception into a practical application. Regarding claims 1-7 and 17-19, no additional elements other than additional microRNAs that are also products of nature are recited. The preamble of “a nutritional composition”, and “wherein the nutritional composition is an infant formula” do not provide additional elements to the body of the claim. While claims 20-21 recite additional components, based on the broadest reasonable interpretation, they include water (which is recited in claim 21) and claim 22 recites additional natural products. Therefore the claims do not recite additional elements that integrate the judicial into a practical application.
Next, Step 2B of the Eligibility Analysis on whether a claim amounts to significantly more than the judicial exception is evaluated. Claims 1-7 and 17-22 do not add significantly more because of generally linking the use of the judicial exception to a particular technological environment or field of use. See MPEP 2106.05(h).
Therefore, it is concluded that claims 1-7 and 17-22 fail all of the steps of the test for subject matter eligibility under 35 USC 101.
Response to Arguments
Applicant's arguments filed 02/27/2026 have been fully considered but they are not persuasive. Applicant argues that independent claim 1 has been amended to recite “the nutritional composition is not natural human or animal milk”.
This is not found persuasive. Amending the claims to recite that the nutritional composition is not natural human or animal milk, does not change the fact that the recited miRNAs as well as the non-digestible oligosaccharide added to claim 1 are naturally occurring products and do not have markedly different characteristics from those found in nature. MPEP 2106.04(b) states: It is important to keep in mind that product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart. See, e.g., Ambry Genetics, 774 F.3d at 760, 113 USPQ2d at 1244 ("Contrary to Myriad's argument, it makes no difference that the identified gene sequences are synthetically replicated. As the Supreme Court made clear, neither naturally occurring compositions of matter, nor synthetically created compositions that are structurally identical to the naturally occurring compositions, are patent eligible."). Thus, a synthetic, artificial, or non-naturally occurring product such as a cloned organism or a human-made hybrid plant is not automatically eligible because it was created by human ingenuity or intervention. See, e.g., In re Roslin Institute (Edinburgh), 750 F.3d 1333, 1337, 110 USPQ2d 1668, 1671-72 (Fed. Cir. 2014) (cloned sheep); cf. J.E.M. Ag Supply, Inc. v. Pioneer Hi-Bred Int’l, Inc., 534 U.S. 130-132, 60 USPQ2d 1868-69 (2001) (hybrid plant). Instead, the key to the eligibility of all non-naturally occurring products is whether they possess markedly different characteristics from any naturally occurring counterpart.
In the instant case, both the recited miRNAs and the non-digestible oligosaccharides and the additional ingredients in claim 22 are each products of nature, and none of the claims recite any characteristics of the recited miRNAs or the non-digestible oligosaccharide or ingredients of claim 22, and therefore they do not have markedly different characteristics from that found in nature and the claims only generally link the use of the judicial exception to a particular technological environment or field of use.
For these reasons, the rejection is maintained.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-7 and 17-22 are rejected under 35 U.S.C. 103 as being unpatentable over Basu et al. (US20130330364, Published 12 Dec 2013), in view of Kim et al. (Clin Exp Pediatr. 2020 March 23, 63(8): 301-309) and Sprenger et al. (WO 2018215189, Published 29 Nov 2018).
Regarding claims 1-3, Basu et al. teach a formulation containing secreted products that are part of a vesicle derived from renal cells, including secreted vesicles, and the secreted vesicles comprise microRNAs, preferably human miRNA, and one or more miRNAs are selected from the group consisting of…….miR-3141….. (paragraphs 0160-0161, pages 15-16). Basu et al. teach the therapeutic renal cell populations or admixtures thereof described herein can be suspended in a pharmaceutically acceptable carrier or excipient, which includes water (paragraph 0242), which reads on the instantly claimed nutritional composition, infant formula, fortifier, and supplement.
Basu et al. does not teach that the formulation is natural human or animal milk.
Basu et al. does not teach a composition comprising at least one non-digestible oligosaccharide.
Before the effective filing date, Kim et al. taught in recent years, various infant formulas have been developed for greater similarity to human breast milk (HBM) and are being supplemented with breast-milk specific ingredients, such as human milk oligosaccharide (HMO) (Introduction, page 301). Kim et al. taught that milk is the most abundant body fluid of RNAs and miRNAs and is known to play a role in various aspects of the infant’s immune system via miRNAs delivered through human breast milk, and there are almost 1,400 different species of mature miRNAs in human breast milk which vary depending on the test method and research between colostrum and mature milk, among milk cell, milk lipid and milk exosomes (page 306, left column). Kim et al. taught that the miRNAs in HBM are thought to be transported to the infant’s intestine through lactation, and appear to reach various tissues and organs through the bloodstream and perform various functions such as immunoprotection and developmental programming, and although miRNAs are also found in high concentrations in animal milk, the infant formula contains few human mature miRNA species which are expressed at much lower levels than in HBM (page 306, left column).
Kim et al. taught with the development of various technologies, humans have been able to replace much of what is available in nature. HBM for infants has also been attempted to be replaced by various artificial milk types. Nevertheless, there is no perfect replacement for HBM yet. Macronutrients, such as carbohydrates, proteins (including immunologic components), fats, various micronutrients, and vitamins, trophic factors, as well as microbiome and miRNA are in the spotlight recently; these are the components of HBM available only in humans and only through lactating mothers, thus making them diverse and irreplaceable (Conclusion, page 306).
Sprenger et al. taught nutritional compositions comprising human milk oligosaccharides for use to decrease the concentration of detrimental proteolytic metabolites (e.g. branched short chain fatty acids) in the digestive tract in infants or young children (Field of Invention, page 1). Sprenger et al. taught decreasing such concentration of detrimental proteolytic metabolites such as ammonium and branched SCFA in the digestive tract is therefore in itself a therapeutic solution. It is an attractive target that also provides positive health advantages (by preventing/treating some health disorders and/or by promoting some health benefits). While mother’s milk is recommended for all infants for various reasons, in some cases breastfeeding is inadequate or unsuccessful for medical reasons or the mother chooses not to breast feed. Infant formula have been developed for these situations. Fortifiers have also been developed to enrich mother's milk or infant formula with specific ingredients. Prebiotics are non-digestible carbohydrates that contribute to the well-being of their host. They are typically compounds that pass undigested through the upper part of the gastrointestinal tract and stimulate the growth and/or activity of advantageous bacteria such as bifidobacteria that colonize the large bowel by acting as substrate for them or via a cross feeding. Human milk oligosaccharides (HMOs) are, collectively, the third largest solid constituents in human milk, after lactose and fat (page 3). Sprenger et al. taught some compositions using HMO ingredients, such as fucosylated oligosaccharides, lacto-N-tetraose, lacto-N-neotetraose and/or sialylated oligosaccharides, have been described for different health purposes, mainly immune purposes. The present inventors believe that a composition comprising at least two human milk oligosaccharides is particularly efficient to decrease the concentration of detrimental proteolytic metabolites such as branched short chain fatty acids in the digestive tract in an infant or a young child (Page 4).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the formulation containing one or more miRNAs of Basu et al. to include at least one human milk oligosaccharide (a non-digestible oligosaccharide) based on the teachings of Kim et al. regarding developing infant formulas supplemented with human breast milk-specific ingredients including miRNAs and human milk oligosaccharide, as well as the teachings of Sprenger et al. regarding the benefits of HMO’s in nutritional compositions including infant formulas to arrive at the instant claims with a reasonable expectation of success. One skilled in the art would at once envisage the miR-3141 from the finite list of miRs of Basu et al. which is specifically taught, and formulate into a nutritional composition based on the teachings of Kim et al. and Sprenger et al. One of ordinary skill in the art would have been motivated to do so because Kim et al. taught there are over 1400 different species of mature miRNAs in human breast milk, and therefore there would be a reasonable expectation of success that miR-3141 is found in human breast milk, and taught that various infant formulas have been developed for greater similarity to human breast milk (HBM) and are being supplemented with breast-milk specific ingredients, such as human milk oligosaccharide (HMO). Therefore, one of ordinary skill in the art would be motivated to provide a composition that is not natural human or animal milk, but that contains miRNAs found in human milk and formulate with additional ingredients such as non-digestible oligosaccharides into a nutritional composition, because Sprenger et al. provides motivation that while mother’s milk is recommended for all infants for various reasons, in some cases breastfeeding is inadequate or unsuccessful for medical reasons or the mother chooses not to breast feed, and therefore infant formula have been developed for these situations and fortifiers have also been developed to enrich mother's milk or infant formula with specific ingredients and taught human milk oligosaccharides for use to decrease the concentration of detrimental proteolytic metabolites in nutritional formulations, including infant formulas which provides positive health advantages. “Disclosure of a multitude of effective combinations does not render any particular formulation less obvious.” Merck & Co. v. Biocraft Laboratories, Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). Note MPEP 2123.
Regarding claim 4, Basu et al. does not recite the exact concentration of 0.1-10000 pmol/L of miR-3141, and regarding claims 5-7, Basu et al. does not explicitly teach the specific combination of miR-3141 and one or more additional microRNAs as recited in instant claims 5-7.
However, regarding claim 4, Basu et al. teach the dosage of the bioactive cell formulations described herein may be calculated based on the estimated mass or functional mass of the target organ or tissue, and the bioactive cell formulation contains a dosage corresponding to a number of cells based upon the weight of the host organ that will be the subject of treatment, and lists different amounts of cells per gram of kidney (paragraphs 0236-0239). Basu et al. teach the formulation may contain a dosage of cells to a subject that is a single dosage or a single dosage plus additional dosages, and the therapeutically effective amount of the renal cell populations described herein can range from the maximal number of cells that is safely received by the subject to the minimum number of cells necessary for treatment (paragraph 0241).
It would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the formulation containing one or more miRNAs of Basu et al. to include at least one human milk oligosaccharide (a non-digestible oligosaccharide) based on the teachings of Kim et al. and the teachings of Sprenger et al. and to provide a concentration of 0.1-10000 pmol/L of miR-3141 in the formulation of Basu et al. modified by Kim et al. and Sprenger et al. based on Basu et al. teaching calculating dosages of cells in the formulations based on different factors including weight of the host organ that will be the subject of treatment, and that the therapeutically effective amount of the renal cell populations described herein can range from the maximal number of cells that is safely received by the subject to the minimum number of cells necessary for treatment. One would be motivated to optimize the concentration of the miR-3141 in the formulation to provide the optimal concentration based on the desired effect.
Additionally, It is generally noted that differences in concentration do not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. "[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). Given that applicant did not point out the criticality of concentration of miR-3141 of the invention, it is concluded that the normal desire of scientists or artisans to improve upon what is already generally known would provide the motivation to determine where in a disclosed set of ranges is the optimum concentration. NOTE: MPEP 2144.05.
Regarding claims 5-7, Basu et al. teach the one or more miRNAs are selected from the group consisting of let-7b, let-7c…miR-19b…miR-22…miR24-1…miR-25…miR-29a..miR30a…miR-92a..miR-99a…miR-100...(paragraph 0160)...miR-197…miR-30d…miR-181a-1...miR-181b-1…miR-205…miR-210…miR-221…miR-125b-2…miR-125a…miR-149…miR-193a…miR-320a…miR-200a…miR-99b…miR-130b…miR-30e…miR-375…miR378…miR-151…miR-425..miR-484…miR-146b…miR-574…miR-652…miR-320c…miR-3184…let-7d… miR-196a…miR-187..miR-516a…miR-92b… miR-3126 (paragraphs 0160-0161, pages 15-16). Basu et al. teach the formulations of the invention may be administered for the treatment of disease (paragraph 0172). Basu et al. teach that those of ordinary skill in the art will appreciate that other miRNAs and combinations of miRNAs may be suitable for use in the present invention (paragraph 0162).
It would have been obvious to one of ordinary skill in the art before the effective filing date, to have combined any of the miRNAs taught by Basu et al. modified by the teachings of Kim et al. and Sprenger et al. to arrive at the instant claims with a reasonable expectation of success. There would be a reasonable expectation of success because Basu et al. teach a formulation comprising one or more of any of the miRs which include let-7b, let-7c…miR-19b…miR-22…miR24-1…miR-25…miR-29a..miR30a…miR-92a..miR-99a…miR-100...(paragraph 0160)...miR-197…miR-30d…miR-181a-1...miR-181b-1…miR-205…miR-210…miR-221…miR-125b-2…miR-125a…miR-149…miR-193a…miR-320a…miR-200a…miR-99b…miR-130b…miR-30e…miR-375…miR378…miR-151…miR-425..miR-484…miR-146b…miR-574…miR-652…miR-320c…miR-3184…let-7d… miR-196a…miR-187..miR-516a…miR-92b… miR-3126, and which are for the same purpose for treatment of a disease (paragraph 0172). One of ordinary skill in the art would have been motivated to provide a combination of miR-3141 an additional microRNAs selected from the group consisting of: let-7b, let-7c…miR-19b…miR-22…miR24-1…miR-25…miR-29a..miR30a…miR-92a..miR-99a…miR-100...(paragraph 0160)...miR-197…miR-30d…miR-181a-1...miR-181b-1…miR-205…miR-210…miR-221…miR-125b-2…miR-125a…miR-149…miR-193a…miR-320a…miR-200a…miR-99b…miR-130b…miR-30e…miR-375…miR378…miR-151…miR-425..miR-484…miR-146b…miR-574…miR-652…miR-320c…miR-3184…let-7d… miR-196a…miR-187..miR-516a…miR-92b… miR-3126; or to provide the combination of miR-3141 and one or more additional microRNAs selected from the group consisting of let-7d, miR-196a, miR-187, miR-516a, miR-92b, miR-3184 and miR-3126, and the combination of miR-3141 with miR-3184 and miR-3126 based on Basu et al. teaching that combinations of the individual miRNAs may be suitable for treatment and that those of ordinary skill in the art will appreciate that other miRNAs and combinations of miRNAs may be suitable for use in the present invention (paragraph 0162) and the teachings of Kim et al. regarding milk being the most abundant body fluid of RNAs and miRNAs and the development of infant formulas supplemented with human breast milk-specific ingredients such as human milk oligosaccharide in order to provide a nutritional composition that is not natural human or animal milk comprising the miRNAs and human milk oligosaccharides for use for those that cannot breast feed.
Regarding claim 17, Basu et al. taught the formulation may be in a substantially solid state at about 8 degree Celsius, and a substantially liquid state at ambient temperature or above.
Basu et al. does not teach the composition in a powder form.
Before the effective filing date, Sprenger et al. taught the nutritional composition of the present invention can be in solid (e.g. powder), liquid or gelatinous form (page 19).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the formulation containing one or more miRNAs of Basu et al. with the teachings of Kim et al. and Sprenger et al. to provide a composition in the form of a solid, including a powder, liquid or gelatinous form based on the teachings of Sprenger et al. One of ordinary skill in the art would have been motivated to do so to provide compositions in different forms for administration, as Basu et al. taught formulations that may be in a substantially solid state at about 8 degree Celsius, and a substantially liquid state at ambient temperature or above, and Sprenger et al. taught nutritional composition in solid (e.g., powder), liquid or gelatinous forms.
Regarding claim 19, Basu et al. does not teach the composition has an energy density of about 60-72 kcal per 100 mL.
Before the effective filing date, Kim et al. taught that human mature breast milk has an energy of 65-70 kcal/100mL and that the proposed composition in cow milk formula has an energy of 60-70kcal/100mL.
It would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the formulation containing the miRNA of Basu et al. with the teachings of Kim et al. and Sprenger et al. and provide a nutritional composition which is an infant formula which is not natural human or animal milk having an energy density of about 60-72 kcal per 100 mL. One of ordinary skill in the art would have been motivated to do so in order to provide a nutritional composition having the same energy density as that of human breast milk or bovine milk formula.
Regarding claims 20 and 21, Sprenger et al. taught the composition of the invention may be a supplement, and that the supplement may be in the form of tablets, capsules, pastilles or a liquid for example. The supplement may further contain protective hydrocolloids (such as gums, proteins, modified starches), binders, film forming agents, encapsulating agents/materials, wall/shell materials, matrix compounds, coatings, emulsifiers, surface active agents, solubilizing agents (oils, fats, waxes, lecithins etc.), adsorbents, carriers, fillers, co-compounds, dispersing agents, wetting agents, processing aids (solvents), flowing agents, taste masking agents, weighting agents, jellifying agents and gel forming agents. The supplement may also contain conventional pharmaceutical additives and adjuvants, excipients and diluents, including, but not limited to, water, gelatine of any origin, vegetable gums, lignin-sulfonate, talc, sugars, starch, gum arabic, vegetable oils, polyalkylene glycols, flavouring agents, preservatives, stabilizers, emulsifying agents, buffers, lubricants, colorants, wetting agents, fillers, and the like (page 23).
Regarding claim 22, Sprenger et al. taught the nutritional composition according to the invention generally contains a protein source, and the type of protein is not believed to be critical to the present invention provided that the minimum requirements for essential amino acid content are met and satisfactory growth is ensured. Thus, protein sources based on whey, casein and mixtures thereof may be used as well as protein sources based on soy (page 19). Sprenger et al. taught the nutritional composition according to the present invention generally contains a carbohydrate source. This is particularly preferable in the case where the nutritional composition of the invention is an infant formula. In this case, any carbohydrate source conventionally found in infant formulae such as lactose, sucrose, saccharose, maltodextrin, starch and mixtures thereof may be used although one of the preferred sources of carbohydrates is lactose (pages 20-21). Sprenger et al. taught the nutritional composition according to the present invention generally contains a source of lipids. This is particularly relevant if the nutritional composition of the invention is an infant formula. In this case, the lipid source may be any lipid or fat which is suitable for use in infant formulae. Some suitable fat sources include palm oil, high oleic sunflower oil and high oleic safflower oil (page 21). The nutritional composition of the invention may also contain all vitamins and minerals understood to be essential in the daily diet and in nutritionally significant amounts (page 21).
It would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the formulation containing the miRNA of Basu et al. with the teachings of Kim et al. and Sprenger et al. and provide the nutritional composition with the additional recited ingredients of claims 20-22 with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Sprenger et al. taught the composition of the invention may be a supplement, that may contain the ingredients recited in claims 20-21, and taught nutritional compositions contain a protein source, carbohydrate source, lipid source, vitamins and minerals is particularly relevant if the nutritional composition of the invention is an infant formula.
Accordingly, the limitations of claims 1-7 and 17-22 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-7 and 17-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,3-7,10,14 and 17-19 of copending Application No. 18015105 (reference application- Notice of Allowance mailed but not yet patented) in view of Kim et al. (Clin Exp Pediatr. 2020 March 23, 63(8): 301-309) and Sprenger et al. (WO 2018215189, Published 29 Nov 2018), cited above.
The copending claims of ‘105 recite a nutritional composition (including infant formula, a fortifier, and a supplement) comprising miR-3126-5p (claim 1), additional microRNAs in claim (5) that include the same microRNAs as in instant claim 5, and that the nutritional composition further comprises miR-3141 and miR-3184 in claim 7. The copending “method of protecting gastrointestinal health…..in a subject” comprises administering a nutritional composition comprising miR-3126 without explicit mention of a composition also comprising miR-3141. However, the copending claims recite nutritional compositions comprising miR-3126 and miR-3141 and miR-3184 (claim 7), and it would be obvious to an artisan that the method of copending claims 10 and 14 can be used with the nutritional compositions of claims 1-7, wherein the composition may further comprise miR-3141.
The copending claims of ‘105 do not recite that the nutritional composition comprises at least one non-digestible oligosaccharide.
The teachings of Kim et al. and Sprenger et al. have been described above in the 103 rejections.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the nutritional composition and method claims of ‘105 to include at least one human milk oligosaccharide (a non-digestible oligosaccharide) based on the teachings of Kim et al. regarding milk being the most abundant body fluid of RNAs and miRNAs and developing infant formulas supplemented with human breast milk-specific ingredients such as human milk oligosaccharide, well as the teachings of Sprenger et al. regarding the benefits of HMO’s in nutritional compositions including infant formulas to arrive at the instant claims with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Kim et al. taught there are over 1400 different species of mature miRNAs in human breast milk, and taught that various infant formulas have been developed for greater similarity to human breast milk (HBM) and are being supplemented with breast-milk specific ingredients, such as human milk oligosaccharide (HMO). In addition, Sprenger et al. provides motivation that while mother’s milk is recommended for all infants for various reasons, in some cases breastfeeding is inadequate or unsuccessful for medical reasons or the mother chooses not to breast feed, and therefore infant formula have been developed for these situations and fortifiers have also been developed to enrich mother's milk or infant formula with specific ingredients and taught human milk oligosaccharides for use to decrease the concentration of detrimental proteolytic metabolites in nutritional formulations, including infant formulas which provides positive health advantages.
The copending claims do not recite the concentration of miR-3141.
Copending claim 4 recites a concentration range of 0.1-10000 pmol/L, 0.1-1000 pmol/L, 1-1000 pmol/L, 10-1000 pmol/L or 100-1000 pmol/L of the miR-3126. It would be obvious to an artisan that this broad concentration range could be applied to any of the miRNA recited by the copending claims, including miR-3141. Therefore, the concentration of miR-3141 of 0.1-10000 pmol/L would be obvious based on the copending claim limitations.
The copending claims do not recite the forms in instant claims 17-18, energy density of claim 19, or additional ingredients recited in instant claims 20-22.
The teachings of Kim et al. and Sprenger et al. have been described above in the 103 rejections.
It would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the nutritional composition of ‘105 with the teachings of Kim et al. and Sprenger et al. and provide a nutritional composition which is an infant formula which is not natural human or animal milk having an energy density of about 60-72 kcal per 100 mL. One of ordinary skill in the art would have been motivated to do so in order to provide a nutritional composition having the same energy density as that of human breast milk or bovine milk formula as taught by Kim et al.
It would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the nutritional composition of ‘105 with the teachings of Kim et al. and Sprenger et al. with the additional recited ingredients of claims 20-22 with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Sprenger et al. taught the composition of the invention may be a supplement, that may contain the ingredients recited in claims 20-21, and taught nutritional compositions contain a protein source, carbohydrate source, lipid source, vitamins and minerals is particularly relevant if the nutritional composition of the invention is an infant formula.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-7 and 17-22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17 and 19-25 of copending Application No. 18015108 (reference application), in view of Kim et al. (Clin Exp Pediatr. 2020 March 23, 63(8): 301-309) and Sprenger et al. (WO 2018215189, Published 29 Nov 2018), cited above.
The copending claims recite a nutritional composition (including infant formula, a fortifier, and a supplement) that is not natural human or animal milk, comprising miR-3184 (claims 17,19-26), miR-3141 (claim 23) and miR-3126 (claims 21-23). The copending method of “promoting healthy growth and development…in a subject” comprises administering a nutritional composition comprising miR-3184, without explicit mention of the composition also comprising miR-3141. However, the copending claims recite nutritional compositions comprising miR-3141 and miR-3126 (claim 23), and it would be obvious to an artisan that the method of copending claims 24-25 can be used with the nutritional composition of claims 17-23, wherein the composition may further comprise miR-3126 and miR-3141.
The copending claims of ‘108 do not recite that the nutritional composition comprises at least one non-digestible oligosaccharide.
The teachings of Kim et al. and Sprenger et al. have been described above in the 103 rejections.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the nutritional composition and method claims of ‘108 to include at least one human milk oligosaccharide (a non-digestible oligosaccharide) based on the teachings of Kim et al. regarding milk being the most abundant body fluid of RNAs and miRNAs and developing infant formulas supplemented with human breast milk-specific ingredients such as human milk oligosaccharide, well as the teachings of Sprenger et al. regarding the benefits of HMO’s in nutritional compositions including infant formulas to arrive at the instant claims with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Kim et al. taught there are over 1400 different species of mature miRNAs in human breast milk, and taught that various infant formulas have been developed for greater similarity to human breast milk (HBM) and are being supplemented with breast-milk specific ingredients, such as human milk oligosaccharide (HMO). In addition, Sprenger et al. provides motivation that while mother’s milk is recommended for all infants for various reasons, in some cases breastfeeding is inadequate or unsuccessful for medical reasons or the mother chooses not to breast feed, and therefore infant formula have been developed for these situations and fortifiers have also been developed to enrich mother's milk or infant formula with specific ingredients and taught human milk oligosaccharides for use to decrease the concentration of detrimental proteolytic metabolites in nutritional formulations, including infant formulas which provides positive health advantages.
The copending claims do not recite the concentration of miR-3141. Copending claim 20 recites a concentration range of 0.1-10000pmol/L of the miR-3184. It would be obvious to an artisan that this broad concentration range could be applied to any of the miRNA recited by the copending claims, including miR3141. Therefore, the concentration of miR-3141 of 0.1-10000 pmol/L would be obvious based on the copending claim limitations.
The copending claims do not recite the forms in instant claims 17-18, energy density of claim 19, or additional ingredients recited in instant claims 20-22.
The teachings of Kim et al. and Sprenger et al. have been described above in the 103 rejections.
It would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the nutritional composition of ‘108 with the teachings of Kim et al. and Sprenger et al. and provide a nutritional composition which is an infant formula which is not natural human or animal milk having an energy density of about 60-72 kcal per 100 mL. One of ordinary skill in the art would have been motivated to do so in order to provide a nutritional composition having the same energy density as that of human breast milk or bovine milk formula as taught by Kim et al.
It would have been obvious to one of ordinary skill in the art before the effective filing date, to modify the nutritional composition of ‘108 with the teachings of Kim et al. and Sprenger et al. with the additional recited ingredients of claims 20-22 with a reasonable expectation of success. One of ordinary skill in the art would have been motivated to do so because Sprenger et al. taught the composition of the invention may be a supplement, that may contain the ingredients recited in claims 20-21, and taught nutritional compositions contain a protein source, carbohydrate source, lipid source, vitamins and minerals is particularly relevant if the nutritional composition of the invention is an infant formula.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant stated on page 8 of response that terminal disclaimers would be premature at this stage in prosecution as the present claims have not yet been allowed and the co-pending applications may also be amended during prosecution, and at such time when the claims of the co-pending application is allowed, Applicant will reconsider the remaining double patenting rejections in view of the allowed claims and requests the double patenting rejections be withdrawn or held in abeyance until the claims are otherwise allowable in the present application.
As the claims are not yet allowable in the present application, the non-statutory double patenting rejections have been modified due to the claim amendments adding at least one non-digestible oligosaccharide, and are held in abeyance.
Conclusion
Claims 1-7 and 17-22 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/STEPHANIE L SULLIVAN/Examiner, Art Unit 1635
/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
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