DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on 08/21/2025 has been entered.
Claims 6-10, 12-15 and 17-24 are pending in this application.
Applicant’s amendment to the claims filed 08/21/2025 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed on 08/21/2025 in response to the final rejection mailed on 03/21/2025 are acknowledged and have been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election
The elected subject matter is:
Invention I, corresponding to claims 12-15 and 17-24, drawn to the technical feature of a product comprising a spray-dried powder of 3’-SL and/or 6’-SL,
elected without traverse in the reply filed 05/16/2023.
Claims 6-10 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
New claims 18-24 are drawn to the composition of claim 12, and are therefore considered drawn to the subject matter of elected Invention I. Claims 12-15 and 17-24 are being examined on the merits.
Claim Rejections - 35 USC § 112(b)
Claim 17 is newly rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 17 is rejected for the recitation of “the product of claim 12”. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 101
Claims 12-15 and 17-24 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Applicant’s attention is directed to the "Guidance for Determining Subject Matter Eligibility Of Claims Reciting Or Involving Laws of Nature, Natural Phenomena, & Natural Products”, released on December 16, 2014.
The instant rejection is maintained from the previous Office Action, and any newly recited portions are necessitated by claim amendment.
Claim Interpretation: As amended, claims 12-15 and 17-24 are drawn to a nutritional composition containing a spray-dried powder comprising at least 80 %-wt of 3’-sialyllactose and/or 6’-sialyllactose, and less than or equal to 5 %-wt of water, wherein the 3’-SL and/or 6’-SL have been produced by microbial fermentation, wherein the nutritional composition comprises at least one probiotic microorganism, and further comprises tyndalized probiotic bacteria.
The limitation of a “spray-dried powder” is considered a product-by-process limitation, wherein the product of the powder is only limited by the structure implied by the step of spray-drying (see MPEP 2113.I), as the instant specification describes the process of spray-drying to be “a method to obtain dry powders, wherein the solution containing the substance of interest is sprayed into droplets which are rapidly dried by hot air” [p 12, lines 6-9]. As Applicant states “the rapid dry process of spray drying permits maintenance of the quality of the materials in the powder, minimizing nutrient loss and can preserve characteristics such as flavor, aroma and color” [p 2, para 1 of the response filed 08/21/2025], the process of spray-drying is not considered to impart any structural or functional characteristics on the material being dehydrated, as (a) the quality of materials being maintained and (b) the minimizing loss and preservation of characteristics indicates that these characteristics as already present before spray-drying.
The instant specification discloses that 3’-SL and 6’-SL are the most abundant sialylated human milk oligosaccharides (HMOs) [p 2, lines 6-7]. According to Thongaram et al. (J Dairy Sci, 2017, 100:7825; cited on the Form PTO-892 mailed 03/21/2025; herein referred to as Thongaram), human milk is known to contain HMO as well as bifidobacterial and lactobacilli that colonize the infant GI tract, and these organisms are considered health promoting microbes [p 7825, col 2, para 2] that are understood in the art as probiotics. Therefore the probiotic recited in the claims are broadly interpreted to encompass naturally occurring organisms such as those disclosed by Thongaram.
Regarding the component of tyndalized probiotic bacterium, the instant specification discloses that tyndalized bacterium can be considered killed bacterial cultures [p 17]. As a probiotic culture as recited in the claims is considered to encompass naturally occurring microorganisms, tyndalized bacteria are similarly drawn to naturally occurring microorganisms, as microorganisms both live and dead are understood to occur naturally.
Given that the composition recited in claims 12-15 and 17-24 is only required to comprise the recited HMO and/or an additional naturally occurring HMO, and an undefined probiotic organism, the composition of claims 12-15 and 17-24 is considered to encompass a naturally occurring composition. Furthermore, as the spray-dried composition as defined by the specification consists of a substance of interest that has been dehydrated, the components of the spray-dried composition that comprise the recited HMOs and probiotics are not considered to be structurally different from their naturally occurring counterparts.
Therefore, given the broadest reasonable interpretation, claims 12-15 and 17-24 are directed to the naturally-occurring human milk oligosaccharide of 3’-SL and/or 6’-SL, a naturally-occurring probiotic bacterium, and a naturally-occurring tyndalized probiotic bacterium.
Patent Eligibility Analysis Step 1: The claims are drawn to a composition of matter, which is one of the statutory categories of invention.
Patent Eligibility Analysis Step 2A Prong 1: The claims recite naturally occurring human milk oligosaccharides 3’-SL and/or 6’-SL and naturally-occurring microorganisms, which are considered to be a law of nature or natural phenomena (natural products). Accordingly, claims 12-15 and 17-24 are directed to a judicial exception.
Patent Eligibility Analysis Step 2A Prong 2: There are no additional elements recited in the claims beyond the judicial exception. There is no indication in the specification or the prior art of record that the claimed composition of HMOs and probiotic bacteria has any characteristics (structural, functional or otherwise) that are different from the individual components as each occurs in nature, particularly in view of Thongaram. In this case, the claimed composition does not have markedly different characteristics from what occurs in nature and is considered to be a “product of nature” exception. Accordingly, composition of claims 12-15 and 17-24 is directed to a judicial exception.
Patent Eligibility Analysis Step 2B: The claims only recite the product of nature, without more and do not include any additional elements that could add significantly more to the judicial exception.
As such, the claims do not qualify as eligible subject matter. For these reasons the claim is rejected under section 101 as being directed to non-statutory subject matter.
Response to Remarks: Beginning on page 1 of Applicant’s response to rejections under 35 U.S.C. 101; Applicant in summary contends that the composition comprising a “a spray-dried powder” is not a product of nature, as spray-drying is a method to obtain a dried product permits maintenance of the quality of the materials in the powder, minimizes nutrient loss, and can preserve characteristics of the material; Applicant further contends that the human milk, alleged by Examiner as a potentially analogous composition to the claimed invention, does not comprise the HMOs or water content of the claimed invention.
Applicant’s remarks are considered and found not convincing.
The claims are interpreted as drawn to a spray-dried powder comprising the recited HMOs, wherein the HMOs were considered to be in a powdered or dehydrated form when considering that spray-drying is a method of forming said powder.
As stated above, the limitation of a “spray-dried powder” is considered a product-by-process limitation, wherein the product of the powder is only limited by the structure implied by the step of spray-drying (see MPEP 2113.I), as the instant specification describes the process of spray-drying to be “a method to obtain dry powders, wherein the solution containing the substance of interest is sprayed into droplets which are rapidly dried by hot air” [p 12, lines 6-9].
As Applicant states “the rapid dry process of spray drying permits maintenance of the quality of the materials in the powder, minimizing nutrient loss and can preserve characteristics such as flavor, aroma and color” [p 2, para 1 of the response filed 08/21/2025], the process of spray-drying is not considered to impart any structural or functional characteristics on the material being dehydrated, as (a) the quality of materials being maintained and (b) the minimizing loss and preservation of characteristics of materials indicates the these characteristics as already present before spray-drying.
However, despite whether 3’-SL and/or 6’-SL are in solid (powder) form or liquid form, the structures of the compounds themselves are disclosed in the specification to be the most abundant sialylated human milk oligosaccharides (HMOs) [p 2, lines 6-7]. The spray-dried powder as claimed is only required to contain one or both of the two recited naturally-occurring HMOs, a probiotic organism, and tyndalized probiotic organisms, and given the broadest reasonable interpretation, the claims are directed to naturally-occurring HMOs 3’-SL and/or 6’-SL, a naturally-occurring probiotic bacterium, and a naturally-occurring tyndalized probiotic bacterium.
Regarding Applicant’s response that the Examiner alleges human milk to be potentially analogous to the claimed invention, wherein human milk would not contain the components of the claimed invention in the amounts recited by the claims, the example of human milk by Thongaram is used in the rejection above to establish that the components of the claimed composition are not only naturally occurring, but would naturally occur together. The rejection of record does not state that the claimed composition encompasses human milk, rather it states there is no indication in the specification or the prior art of record that the claimed composition of HMOs and probiotic bacteria has any characteristics (structural, functional or otherwise) that are different from the individual components as each occurs in nature, and therefore the claimed composition does not have markedly different characteristics from what occurs in nature and is considered to be a “product of nature” exception.
Claim Rejections - 35 USC § 103
The rejection of claims 1-3, 5, 11 and 17 under 35 U.S.C. 103 as being unpatentable over Shroven et al. (WO2013185780; cited on the Form PTO-892 mailed 01/08/2024; herein referred to as Shroven) is withdrawn in view of the cancelation of claims 1-3, 5 and 11 and the amendment to claim 17 to depend from claim 12.
Claims 12-15 are rejected under 35 U.S.C. 103 as being unpatentable over Shroven in view of Thongaram and Melnik et al. (Clin Transl Allergy, 2016, 6:18; cited on the Form PTO-892 mailed 03/21/2025; herein Melnik) and evidentiary reference WO 2011/100979 (cited on the Form PTO-892 mailed 01/08/2024; herein Figueroa).
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Claim 12 is drawn to a nutritional composition containing a spray-dried powder, wherein the spray-dried powder comprises
(i) at least 80%-wt of 3'-sialvllactose (3'-SL) and/or 6'-sialvllactose (6'-SL); and
(ii) < 5%-wt. of water,
wherein the 3'-SL and/or 6'-SL have been produced by microbial fermentation;
wherein the nutritional composition comprises at least one probiotic microorganism, and further comprises tyndalized probiotic bacteria.
The limitation of a “spray-dried powder” is considered a product-by-process limitation, wherein the product of the powder is only limited by the structure implied by the step of spray-drying (see MPEP 2113.I), as the instant specification describes the process of spray-drying to be “a method to obtain dry powders, wherein the solution containing the substance of interest is sprayed into droplets which are rapidly dried by hot air” [p 12, lines 6-9]. As Applicant states “the rapid dry process of spray drying permits maintenance of the quality of the materials in the powder, minimizing nutrient loss and can preserve characteristics such as flavor, aroma and color” [p 2, para 1 of the response filed 08/21/2025], the process of spray-drying is not considered to impart any structural or functional characteristics on the material being dehydrated, as (a) the quality of materials being maintained and (b) the minimizing loss and preservation of characteristics of materials indicates the these characteristics as already present before spray-drying.
The recitation of “3'-SL and/or 6'- SL have been produced by microbial fermentation” in claim 1 is interpreted as a product-by-process limitation, wherein the product is not limited by the manipulations of the recited steps (MPEP 2113), as the claimed product of a spray-dried powder comprising 3’-SL and/or 6’-SL appears to the same product disclosed by Shroven as described on p 9, lines 10-13 and p 8 lines 3-8.
Shroven discusses enhancing the stability and purity and increasing the bioavailability of human milk oligosaccharides or precursor [title]. Shroven describes the motivation in the field for making industrial quantities of different HMOs to be for the discovery of their uses in nutritional and therapeutic formulations [p 2, para 1].
Regarding claim 12 and the limitation of the spray-dried composition comprising at least 80%-wt 3’-SL and/or 6’-SL and less or equal to 5%-wt water, Shroven describes methods of providing an HMO in an aqueous solution, wherein the HMO is at a concentration up to 60 wt %, and removing substantially all of the water via spray-drying, particularly at least about 95% of the water to provide the HMO precursor blend with a higher glass temperature of at least 40 °C [p 3, final para to p 5, first para], wherein a glass temperature is a function of water content, and a glass temperature of at least 40 °C is associated with a water content of 4-6% or less [p 9, para 4]. Therefore Shroven teaches the removal of at least 95% of the water of the aqueous solution of HMO to achieve increasingly high glass temperatures associated with such water content, and therefore the resulting spray-dried HMO is understood to contain 5% water or less as recited in the claim.
Shroven further teaches the HMO can be any of a group consisting of 3'-SL and 6'-SL [p 8, lines 3-8]. While Shroven does not explicitly disclose the spray-dried powder of at least 80% 3’-SL and/or 6’-SL as recited in the claim 12, one of ordinary skill in the art would reasonably conclude that carrying out the method of Shroven and removing substantially all of the water from an aqueous solution comprising an HMO would increase the wt % of said HMO to the recited wt % of the claim. Put another way, carrying out the method of Shroven on an aqueous mixture of 60 wt-% HMO to remove substantially all of the water will reduce the total weight of the mixture, thereby increasing wt-% of the HMO to the claimed range, as one of skill in the art would be motivated to remove increasing amounts of water in order to increase the glass temperature of the powder, in order to produce quantities of HMOs to discover their uses in nutritional and therapeutic formulations as taught by Shroven.
Shroven does not teach the inclusion of at least one probiotic and tyndalized probiotics.
Thongaram relates to HMO consumption by probiotic and human-associated bifidobacterial and lactobacilli [title], and discusses that human milk contains HMOs as well as bifidobacterial and lactobacilli that readily colonize the infant GI tract [p 7825, col 2, para 2].
Regarding claim 12, Thongaram teaches that formula-fed infants lack exposure to the health-promoting oligosaccharides and microbes found in human milk, and therefore emphasizes the importance of the delivery of HMOs and probiotic bacteria in infant formula [p 7825, col 2, para 2].
Melnik relates to milk and the postnatal imprinting system stabilizing regulatory T cell (Treg) differentiation [title], and discusses that breastfeeding has protective effects or the development of allergies and atopy, and identifies the biological role of milk controlling stabilized Treg differentiation [abstract]. While Melnik refers to cow’s milk, the findings of Melnik are related to the immunological benefits of children who consume said milk throughout development [p 1, col 1, para 1].
Regarding claim 12, Melnik teaches that the heat-killed probiotic L. pentosus strain S-PT84 was able to exhibit anti-allergic effects through the modulation of Th1/Th2 balance and Treg induction, as well as that both live and heat-killed probiotic L. rhamnosus could induce the anti-inflammatory cytokine IL-10 [p 4, col 2, para 2], wherein heat-killed cultures are understood as tyndalized cultures according to the specification [p 17].
In view of Shroven, Thongaram and Melnik, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the composition of Shroven by including probiotics, as taught by Thongaram, and tyndalized probiotics, as taught by Melnik, to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to modify the composition of Shroven by including the probiotics of Thongaram and Melnik, because Melnik teaches that breastfeeding has protective effects or the development of allergies and atopy related to stabilized Treg differentiation, and Thongaram teaches formula-fed infants lack exposure to the health-promoting oligosaccharides and microbes found in human milk, and therefore emphasizes the importance of the delivery of HMOs and probiotic bacteria in infant formula.
One of ordinary skill in the art would have had a reasonable expectation of success because Shroven and Thongaram relate to compositions of HMOs, and Thongaram and Melnik relate to the benefits of probiotic exposure to developing infants.
Regarding claim 13, Shroven teaches the method can be applied to HMO blends that include a mixture of two or more HMOs that include 3’-SL and 6’-SL which are sialylated HMOs, and 2’-FL [p 98, lines 14-20], wherein 2’-FL is a neutral HMO as evidenced by the instant specification [p 13, lines 11-18].
Regarding claim 14, Shroven teaches the method can be applied to HMO blends that include a mixture of two or more HMOs that include 2’-FL [p 8, lines 14-20], wherein 2’-FL is a neutral HMO as evidenced by the instant specification [p 13, lines 11-18]).
Regarding claim 15, Shroven teaches the method can be applied to HMO blends that include a mixture of two or more HMOs that include 3’-SL and 6’-SL [p 8, lines 14-20] which are sialylated HMOs.
Regarding claims 17 and 23, Shroven teaches the use of the amorphous HMO powder obtained by the disclosed method for making nutritional formulations intended for use with infants [p 10, lines 14-15] which encompasses the limitations of an infant formula recited in claim 17 and amorphous 3’-SL and/or 6’-SL recited in claim 23.
Regarding claims 18-22, Shroven teaches the method discussed in the rejection of claim 12 above, comprising providing an HMO in an aqueous solution, wherein the HMO is at a concentration up to 60 wt %, and removing substantially all of the water via spray-drying, particularly at least about 95% of the water to provide the HMO precursor blend with a higher glass temperature of at least 40 °C [p 3, final para to p 5, first para], wherein a glass temperature is a function of water content, and a glass temperature of at least 40 °C is associated with a water content of 4-6% or less [p 9, para 4]. Therefore Shroven teaches the removal of at least 95% of the water of the aqueous solution of HMO to achieve increasingly high glass temperatures associated with such water content, and therefore the resulting spray-dried HMO is understood to contain 5% water or less.
While Shroven does not explicitly disclose the spray-dried powder of at least 85% 3’-SL and/or 6’-SL (as recited in the claim 18), at least 90% 3’-SL and/or 6’-SL (as recited in the claim 19), at least 93% 3’-SL and/or 6’-SL (as recited in the claim 20), at least 95% 3’-SL and/or 6’-SL (as recited in the claim 21) and at least 98% 3’-SL and/or 6’-SL (as recited in the claim 22), one of ordinary skill in the art would reasonably conclude that carrying out the method of Shroven and removing substantially all of the water from an aqueous solution comprising an HMO would increase the wt % of said HMO to the recited wt % of claims 18-22.
Additionally, MPEP 2144.05.II.A states differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. As Shroven discloses a spray dried mixture of HMOs with substantially all water removed, and provides a motivation for increasing concentrations of said HMOs in the mixture in order to produce quantities of HMOs to discover their uses in nutritional and therapeutic formulations, it would have been obvious to utilize the method of Shroven to increase the concentrations of HMOs to the ranges recited in the claims 18-22 through routine optimization.
Regarding claim 24, Shroven teaches the spray-drying of 6’-SL that is the sodium salt of the benzyl glycoside of 6’-SL synthesized according to WO 2011/100979 [p 14, “Example 3”], wherein the method of WO 2011/100979 is a chemical synthesis method [see Figueroa, p 3, “Summary of Invention”]. As the 6’-SL of Shroven is the result of chemical synthesis, the spray-dried mixture of Shroven is considered free of nucleic acid molecules derived from genetically-engineered microorganisms.
Additionally, Thongaram relates to human-associated bifidobacterial and lactobacilli, which are considered to be naturally-occurring bacteria [title], therefore the combined spray-dried mixture of Shroven, Thongaram and Melnik is considered free of genetically-engineered microorganisms, and thus also free of nucleic acid molecules derived from genetically-engineered microorganisms.
Therefore, the method of claims 12-15 and 17-24 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to Remarks: Beginning on page 3 of Applicant’s response to rejections under 35 U.S.C. 103; Applicant in summary contends the prior traversal is maintained, and the instant amended claim set obviates the rejections under 35 USC 103.
Applicant’s remarks are considered and found not convincing. The response to traversal of previous rejections under 35 USC 103 can be found in the Final rejection mailed 03/21/2025. The rejections of record are maintained as stated in the section above, and updated to reflect any amendments to the claims.
Double Patenting
The rejection of claims 1-3, 5, 11 and 17 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4 and 11-13 of U.S. Patent No. 11,582,994 (cited on the Form PTO-892 mailed 03/21/2025) in view of Shroven,
the rejection of claims 1-3, 5, 11 and 17 on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 10,435,427 (cited on the attached Form PTO-892 mailed) in view of Shroven,
the rejection of claims 1-3, 5, 11 and 17 on the ground of nonstatutory double patenting as being unpatentable over claims 12-16 and 18 of copending Application No. 17/992331 in view of Shroven, and
the rejection of claims 1-3, 5, 11 and 17 on the ground of nonstatutory double patenting as being unpatentable over claims 30-32 of copending Application No. 18/417034 in view of Shroven,
are withdrawn in view of the cancelation of claims 1-3, 5 and 11 and the amendment to claim 17 to depend from claim 12.
The previous provisional double patenting rejections over copending Application No. 18/417034 were previously cited incorrectly as over Application No. 18/417032. The claims and subject matter of the correct Application No. 18/417034 are the same as those recited in the previous provisional rejection over the incorrectly cited Application No. 18/417032.
A. Claims 12-15 and 17-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4 and 11-13 of U.S. Patent No. 11,582,994 (herein “patent”) in view of Shroven, Thongaram, Melnik and evidentiary reference Figueroa.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 12, claim 1 of the patent recites a nutritional composition comprising a spray-dried powder of at least 80% 3-fucosyllactose produced by microbial fermentation. Claim 4 of the patent recites the spray-dried powder comprises less than or equal to 7%-wt. of water. Claim 13 of the patent recites a composition comprising 3’-SL or 6’-SL.
The claims of the patent do not recite a spray-dried powder comprising 3’-SL and/or 6’-SL, probiotic bacteria and tyndalized probiotic bacteria.
Shroven discusses enhancing the stability and purity and increasing the bioavailability of human milk oligosaccharides or precursor [title]. Shroven describes the motivation in the field for making industrial quantities of different HMOs to be for the discovery of their uses in nutritional and therapeutic formulations [p 2, para 1].
Regarding instant claim 12 and the limitation of the spray-dried composition comprising at least 80%-wt 3’-SL and/or 6’-SL and less or equal to 5%-wt water, Shroven describes methods of providing an HMO in an aqueous solution, wherein the HMO is at a concentration up to 60 wt %, and removing substantially all of the water via spray-drying, particularly at least about 95% of the water to provide the HMO precursor blend with a higher glass temperature of at least 40 °C [p 3, final para to p 5, first para], wherein a glass temperature is a function of water content, and a glass temperature of at least 40 °C is associated with a water content of 4-6% or less [p 9, para 4]. Therefore Shroven discloses the removal of at least 95% of the water of the aqueous solution of HMO to achieve increasingly high glass temperatures associated with such water content, and therefore the resulting spray-dried HMO is understood to contain 5% water or less as recited in the claim.
Shroven further discloses the HMO can be any of a group consisting of 3'-SL and 6'-SL [p 8, lines 3-8]. While Shroven does not explicitly disclose the spray-dried powder of at least 80% 3’-SL and/or 6’-SL as recited in the claim 12, one of ordinary skill in the art would reasonably conclude that carrying out the method of Shroven and removing substantially all of the water from an aqueous solution comprising an HMO would increase the wt % of said HMO to the recited wt % of the claim. Put another way, carrying out the method of Shroven on an aqueous mixture of 60 wt-% HMO to remove substantially all of the water will reduce the total weight of the mixture, thereby increasing wt-% of the HMO to the claimed range, as one of skill in the art would be motivated to remove increasing amounts of water in order to increase the glass temperature of the powder, in order to produce quantities of HMOs to discover their uses in nutritional and therapeutic formulations as disclosed by Shroven.
Thongaram relates to HMO consumption by probiotic and human-associated bifidobacterial and lactobacilli [title], and discusses that human milk contains HMOs as well as bifidobacterial and lactobacilli that readily colonize the infant GI tract [p 7825, col 2, para 2].
Regarding instant claim 12, Thongaram discloses that formula-fed infants lack exposure to the health-promoting oligosaccharides and microbes found in human milk, and therefore emphasizes the importance of the delivery of HMOs and probiotic bacteria in infant formula [p 7825, col 2, para 2].
Melnik relates to milk and the postnatal imprinting system stabilizing regulatory T cell (Treg) differentiation [title], and discusses that breastfeeding has protective effects or the development of allergies and atopy, and identifies the biological role of milk controlling stabilized Treg differentiation [abstract]. While Melnik refers to cow’s milk, the findings of Melnik are related to the immunological benefits of children who consume said milk throughout development [p 1, col 1, para 1].
Regarding instant claim 12, Melnik discloses that the heat-killed probiotic L. pentosus strain S-PT84 was able to exhibit anti-allergic effects through the modulation of Th1/Th2 balance and Treg induction, as well as that both live and heat-killed probiotic L. rhamnosus could induce the anti-inflammatory cytokine IL-10 [p 4, col 2, para 2], wherein heat-killed cultures are understood as tyndalized cultures according to the specification [p 17].
In view of Shroven, Thongaram and Melnik, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent by replacing the 3-fucosyllactose with the 3’-SL and/or 6’ SL of Shroven, since the simple substitution of one known element for another results in a predictable result, and by adding the probiotics of Thongaram and tyndalized probiotics of Melnik, to arrive at the claimed invention.
One of ordinary skill in the art would have recognized that both 3’-fucosyllactose and 3’-SL and/or 6’-SL are HMOs used for the formulation of nutritional compositions, and as such both are capable of being incorporated into such compositions as described by the patent. Thus it would have been obvious to one of ordinary skill in the art to replace 3’-fucosyllactose with 3’-SL and/or 6’-SL, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the patent and Shroven discuss nutritional compositions comprised of spray-dried HMOs.
One of ordinary skill in the art would have been motivated to modify the claims of the patent by including the probiotics of Thongaram and Melnik, because Melnik discloses that breastfeeding has protective effects or the development of allergies and atopy related to stabilized Treg differentiation, and Thongaram discloses formula-fed infants lack exposure to the health-promoting oligosaccharides and microbes found in human milk, and therefore emphasizes the importance of the delivery of HMOs and probiotic bacteria in infant formula.
One of ordinary skill in the art would have had a reasonable expectation of success because the patent, Shroven and Thongaram relate to compositions of HMOs, and Thongaram and Melnik relate to the benefits of probiotic exposure to developing infants.
Regarding instant claim 13, Shroven discloses the method can be applied to HMO blends that include a mixture of two or more HMOs that include 3’-SL and 6’-SL which are sialylated HMOs, and 2’-FL [p 98, lines 14-20], wherein 2’-FL is a neutral HMO as evidenced by the instant specification [p 13, lines 11-18].
Regarding instant claim 14, Shroven discloses the method can be applied to HMO blends that include a mixture of two or more HMOs that include 2’-FL [p 8, lines 14-20], wherein 2’-FL is a neutral HMO as evidenced by the instant specification [p 13, lines 11-18]).
Regarding instant claim 15, Shroven discloses the method can be applied to HMO blends that include a mixture of two or more HMOs that include 3’-SL and 6’-SL [p 8, lines 14-20] which are sialylated HMOs.
Regarding instant claims 17 and 23, Shroven discloses the use of the amorphous HMO powder obtained by the disclosed method for making nutritional formulations intended for use with infants [p 10, lines 14-15] which encompasses the limitation of an infant formula recited in claim 17.
Regarding instant claims 18-22, Shroven discloses the method discussed in the rejection of claim 12 above, comprising providing an HMO in an aqueous solution, wherein the HMO is at a concentration up to 60 wt %, and removing substantially all of the water via spray-drying, particularly at least about 95% of the water to provide the HMO precursor blend with a higher glass temperature of at least 40 °C [p 3, final para to p 5, first para], wherein a glass temperature is a function of water content, and a glass temperature of at least 40 °C is associated with a water content of 4-6% or less [p 9, para 4]. Therefore Shroven discloses the removal of at least 95% of the water of the aqueous solution of HMO to achieve increasingly high glass temperatures associated with such water content, and therefore the resulting spray-dried HMO is understood to contain 5% water or less.
While Shroven does not explicitly disclose the spray-dried powder of at least 85% 3’-SL and/or 6’-SL (as recited in the claim 18), at least 90% 3’-SL and/or 6’-SL (as recited in the instant claim 19), at least 93% 3’-SL and/or 6’-SL (as recited in the instant claim 20), at least 95% 3’-SL and/or 6’-SL (as recited in the instant claim 21) and at least 98% 3’-SL and/or 6’-SL (as recited in the instant claim 22), one of ordinary skill in the art would reasonably conclude that carrying out the method of Shroven and removing substantially all of the water from an aqueous solution comprising an HMO would increase the wt % of said HMO to the recited wt % of claims 18-22.
Additionally, MPEP 2144.05.II.A states 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. As Shroven discloses a spray dried mixture of HMOs with substantially all water removed, and provides a motivation for increasing concentrations of said HMOs in the mixture in order to produce quantities of HMOs to discover their uses in nutritional and therapeutic formulations, it would have been obvious to utilize the method of Shroven to increase the concentrations of HMOs to the ranges recited in the instant claims 18-22 through routine optimization.
Regarding instant claim 24, Shroven discloses the spray-drying of 6’-SL that is the sodium salt of the benzyl glycoside of 6’-SL synthesized according to WO 2011/100979 [p 14, “Example 3”], wherein the method of WO 2011/100979 is a chemical synthesis method [see Figueroa, p 3, “Summary of Invention”]. As the 6’-SL of Shroven is the result of chemical synthesis, the spray-dried mixture of Shroven is considered free of nucleic acid molecules derived from genetically-engineered microorganisms.
Additionally, Thongaram relates to human-associated bifidobacterial and lactobacilli, which are considered to be naturally-occurring bacteria [title], the combined spray-dried mixture of Shroven, Thongaram and Melnik is considered free of genetically-engineered microorganisms, and therefore also free of nucleic acid molecules derived from genetically-engineered microorganisms.
B. Claims 12-15 and 17-24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 10 of U.S. Patent No. 10,435,427 (herein “patent”) in view of Shroven, Thongaram, Melnik and evidentiary reference Figueroa.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 12, claim 10 of the patent recites a process of purifying HMO from crude solution wherein the composition is further spray-dried to obtain purified neutral HMO.
The claims of the patent do not recite the limitations that the spray-dried powder comprising at least 80 % of 3’-SL and/or 6’-SL, less than or equal to 5 % water, probiotic bacteria and tyndalized probiotic bacteria.
Shroven discusses enhancing the stability and purity and increasing the bioavailability of human milk oligosaccharides or precursor [title]. Shroven describes the motivation in the field for making industrial quantities of different HMOs to be for the discovery of their uses in nutritional and therapeutic formulations [p 2, para 1].
Regarding instant claim 12 and the limitation of the spray-dried composition comprising at least 80%-wt 3’-SL and/or 6’-SL and less or equal to 5%-wt water, Shroven describes methods of providing an HMO in an aqueous solution, wherein the HMO is at a concentration up to 60 wt %, and removing substantially all of the water via spray-drying, particularly at least about 95% of the water to provide the HMO precursor blend with a higher glass temperature of at least 40 °C [p 3, final para to p 5, first para], wherein a glass temperature is a function of water content, and a glass temperature of at least 40 °C is associated with a water content of 4-6% or less [p 9, para 4]. Therefore Shroven discloses the removal of at least 95% of the water of the aqueous solution of HMO to achieve increasingly high glass temperatures associated with such water content, and therefore the resulting spray-dried HMO is understood to contain 5% water or less as recited in the claim.
Shroven further discloses the HMO can be any of a group consisting of 3'-SL and 6'-SL [p 8, lines 3-8]. While Shroven does not explicitly disclose the spray-dried powder of at least 80% 3’-SL and/or 6’-SL as recited in the claim 12, one of ordinary skill in the art would reasonably conclude that carrying out the method of Shroven and removing substantially all of the water from an aqueous solution comprising an HMO would increase the wt % of said HMO to the recited wt % of the claim. Put another way, carrying out the method of Shroven on an aqueous mixture of 60 wt-% HMO to remove substantially all of the water will reduce the total weight of the mixture, thereby increasing wt-% of the HMO to the claimed range, as one of skill in the art would be motivated to remove increasing amounts of water in order to increase the glass temperature of the powder, in order to produce quantities of HMOs to discover their uses in nutritional and therapeutic formulations as disclosed by Shroven.
Thongaram relates to HMO consumption by probiotic and human-associated bifidobacterial and lactobacilli [title], and discusses that human milk contains HMOs as well as bifidobacterial and lactobacilli that readily colonize the infant GI tract [p 7825, col 2, para 2].
Regarding instant claim 12, Thongaram discloses that formula-fed infants lack exposure to the health-promoting oligosaccharides and microbes found in human milk, and therefore emphasizes the importance of the delivery of HMOs and probiotic bacteria in infant formula [p 7825, col 2, para 2].
Melnik relates to milk and the postnatal imprinting system stabilizing regulatory T cell (Treg) differentiation [title], and discusses that breastfeeding has protective effects or the development of allergies and atopy, and identifies the biological role of milk controlling stabilized Treg differentiation [abstract]. While Melnik refers to cow’s milk, the findings of Melnik are related to the immunological benefits of children who consume said milk throughout development [p 1, col 1, para 1].
Regarding instant claim 12, Melnik discloses that the heat-killed probiotic L. pentosus strain S-PT84 was able to exhibit anti-allergic effects through the modulation of Th1/Th2 balance and Treg induction, as well as that both live and heat-killed probiotic L. rhamnosus could induce the anti-inflammatory cytokine IL-10 [p 4, col 2, para 2], wherein heat-killed cultures are understood as tyndalized cultures according to the specification [p 17].
In view of Shroven, Thongaram and Melnik, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the patent by replacing the neutral HMOs with the 3’-SL and/or 6’ SL of Shroven, since the simple substitution of one known element for another results in a predictable result, and by adding the probiotics of Thongaram and tyndalized probiotics of Melnik, to arrive at the claimed invention.
One of ordinary skill in the art would have recognized that both neutral HMOs and 3’-SL and/or 6’-SL are HMOs used for the formulation of nutritional compositions, and as such both are capable of being incorporated into such compositions as described by the patent. Thus it would have been obvious to one of ordinary skill in the art to replace neutral HMOs with 3’-SL and/or 6’-SL, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the patent and Shroven discuss nutritional compositions comprised of spray-dried HMOs.
One of ordinary skill in the art would have been motivated to modify the claims of the patent by including the probiotics of Thongaram and Melnik, because Melnik discloses that breastfeeding has protective effects or the development of allergies and atopy related to stabilized Treg differentiation, and Thongaram discloses formula-fed infants lack exposure to the health-promoting oligosaccharides and microbes found in human milk, and therefore emphasizes the importance of the delivery of HMOs and probiotic bacteria in infant formula.
One of ordinary skill in the art would have had a reasonable expectation of success because the patent, Shroven and Thongaram relate to compositions of HMOs, and Thongaram and Melnik relate to the benefits of probiotic exposure to developing infants.
Regarding instant claim 13, Shroven discloses the method can be applied to HMO blends that include a mixture of two or more HMOs that include 3’-SL and 6’-SL which are sialylated HMOs, and 2’-FL [p 98, lines 14-20], wherein 2’-FL is a neutral HMO as evidenced by the instant specification [p 13, lines 11-18].
Regarding instant claim 14, Shroven discloses the method can be applied to HMO blends that include a mixture of two or more HMOs that include 2’-FL [p 8, lines 14-20], wherein 2’-FL is a neutral HMO as evidenced by the instant specification [p 13, lines 11-18]).
Regarding instant claim 15, Shroven discloses the method can be applied to HMO blends that include a mixture of two or more HMOs that include 3’-SL and 6’-SL [p 8, lines 14-20] which are sialylated HMOs.
Regarding instant claims 17 and 23, Shroven discloses the use of the amorphous HMO powder obtained by the disclosed method for making nutritional formulations intended for use with infants [p 10, lines 14-15] which encompasses the limitation of an infant formula recited in claim 17.
Regarding instant claims 18-22, Shroven discloses the method discussed in the rejection of claim 12 above, comprising providing an HMO in an aqueous solution, wherein the HMO is at a concentration up to 60 wt %, and removing substantially all of the water via spray-drying, particularly at least about 95% of the water to provide the HMO precursor blend with a higher glass temperature of at least 40 °C [p 3, final para to p 5, first para], wherein a glass temperature is a function of water content, and a glass temperature of at least 40 °C is associated with a water content of 4-6% or less [p 9, para 4]. Therefore Shroven discloses the removal of at least 95% of the water of the aqueous solution of HMO to achieve increasingly high glass temperatures associated with such water content, and therefore the resulting spray-dried HMO is understood to contain 5% water or less.
While Shroven does not explicitly disclose the spray-dried powder of at least 85% 3’-SL and/or 6’-SL (as recited in the claim 18), at least 90% 3’-SL and/or 6’-SL (as recited in the instant claim 19), at least 93% 3’-SL and/or 6’-SL (as recited in the instant claim 20), at least 95% 3’-SL and/or 6’-SL (as recited in the instant claim 21) and at least 98% 3’-SL and/or 6’-SL (as recited in the instant claim 22), one of ordinary skill in the art would reasonably conclude that carrying out the method of Shroven and removing substantially all of the water from an aqueous solution comprising an HMO would increase the wt % of said HMO to the recited wt % of claims 18-22.
Additionally, MPEP 2144.05.II.A states 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. As Shroven discloses a spray dried mixture of HMOs with substantially all water removed, and provides a motivation for increasing concentrations of said HMOs in the mixture in order to produce quantities of HMOs to discover their uses in nutritional and therapeutic formulations, it would have been obvious to utilize the method of Shroven to increase the concentrations of HMOs to the ranges recited in the instant claims 18-22 through routine optimization.
Regarding instant claim 24, Shroven discloses the spray-drying of 6’-SL that is the sodium salt of the benzyl glycoside of 6’-SL synthesized according to WO 2011/100979 [p 14, “Example 3”], wherein the method of WO 2011/100979 is a chemical synthesis method [see Figueroa, p 3, “Summary of Invention”]. As the 6’-SL of Shroven is the result of chemical synthesis, the spray-dried mixture of Shroven is considered free of nucleic acid molecules derived from genetically-engineered microorganisms.
Additionally, Thongaram relates to human-associated bifidobacterial and lactobacilli, which are considered to be naturally-occurring bacteria [title], the combined spray-dried mixture of Shroven, Thongaram and Melnik is considered free of genetically-engineered microorganisms, and therefore also free of nucleic acid molecules derived from genetically-engineered microorganisms.
C. Claims 12-15 and 17-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12-16 and 18 of copending Application No. 17/992331 (herein “reference application”) in view of Shroven, Thongaram, Melnik and evidentiary reference Figueroa.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 12, claim 12 of the reference application recites a nutritional composition comprising a spray-dried powder comprising >95% LNT and/or LNnT which has been produced by microbial fermentation and < 5 %-wt water.
The claims of the reference application do not recite the limitations that the spray-dried powder comprising 3’-SL and/or 6’-SL, and tyndalized probiotic bacteria.
Shroven discusses enhancing the stability and purity and increasing the bioavailability of human milk oligosaccharides or precursor [title]. Shroven describes the motivation in the field for making industrial quantities of different HMOs to be for the discovery of their uses in nutritional and therapeutic formulations [p 2, para 1].
Regarding instant claim 12 and the limitation of the spray-dried composition comprising at least 80%-wt 3’-SL and/or 6’-SL and less or equal to 5%-wt water, Shroven describes methods of providing an HMO in an aqueous solution, wherein the HMO is at a concentration up to 60 wt %, and removing substantially all of the water via spray-drying, particularly at least about 95% of the water to provide the HMO precursor blend with a higher glass temperature of at least 40 °C [p 3, final para to p 5, first para], wherein a glass temperature is a function of water content, and a glass temperature of at least 40 °C is associated with a water content of 4-6% or less [p 9, para 4]. Therefore Shroven discloses the removal of at least 95% of the water of the aqueous solution of HMO to achieve increasingly high glass temperatures associated with such water content, and therefore the resulting spray-dried HMO is understood to contain 5% water or less as recited in the claim.
Shroven further discloses the HMO can be any of a group consisting of 3'-SL and 6'-SL [p 8, lines 3-8]. While Shroven does not explicitly disclose the spray-dried powder of at least 80% 3’-SL and/or 6’-SL as recited in the claim 12, one of ordinary skill in the art would reasonably conclude that carrying out the method of Shroven and removing substantially all of the water from an aqueous solution comprising an HMO would increase the wt % of said HMO to the recited wt % of the claim. Put another way, carrying out the method of Shroven on an aqueous mixture of 60 wt-% HMO to remove substantially all of the water will reduce the total weight of the mixture, thereby increasing wt-% of the HMO to the claimed range, as one of skill in the art would be motivated to remove increasing amounts of water in order to increase the glass temperature of the powder, in order to produce quantities of HMOs to discover their uses in nutritional and therapeutic formulations as disclosed by Shroven.
Thongaram relates to HMO consumption by probiotic and human-associated bifidobacterial and lactobacilli [title], and discusses that human milk contains HMOs as well as bifidobacterial and lactobacilli that readily colonize the infant GI tract [p 7825, col 2, para 2].
Regarding instant claim 12, Thongaram discloses that formula-fed infants lack exposure to the health-promoting oligosaccharides and microbes found in human milk, and therefore emphasizes the importance of the delivery of HMOs and probiotic bacteria in infant formula [p 7825, col 2, para 2].
Melnik relates to milk and the postnatal imprinting system stabilizing regulatory T cell (Treg) differentiation [title], and discusses that breastfeeding has protective effects or the development of allergies and atopy, and identifies the biological role of milk controlling stabilized Treg differentiation [abstract]. While Melnik refers to cow’s milk, the findings of Melnik are related to the immunological benefits of children who consume said milk throughout development [p 1, col 1, para 1].
Regarding instant claim 12, Melnik discloses that the heat-killed probiotic L. pentosus strain S-PT84 was able to exhibit anti-allergic effects through the modulation of Th1/Th2 balance and Treg induction, as well as that both live and heat-killed probiotic L. rhamnosus could induce the anti-inflammatory cytokine IL-10 [p 4, col 2, para 2], wherein heat-killed cultures are understood as tyndalized cultures according to the specification [p 17].
In view of Shroven, Thongaram and Melnik, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the reference application by replacing the LNT with the 3’-SL and/or 6’ SL of Shroven, since the simple substitution of one known element for another results in a predictable result, and by adding the probiotics of Thongaram and tyndalized probiotics of Melnik, to arrive at the claimed invention.
One of ordinary skill in the art would have recognized that both LNT and 3’-SL and/or 6’-SL are HMOs used for the formulation of nutritional compositions, and as such both are capable of being incorporated into such compositions as described by the reference application. Thus it would have been obvious to one of ordinary skill in the art to replace LNT with 3’-SL and/or 6’-SL, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Shroven discuss nutritional compositions comprised of spray-dried HMOs.
One of ordinary skill in the art would have been motivated to modify the claims of the reference application by including the probiotics of Thongaram and Melnik, because Melnik discloses that breastfeeding has protective effects or the development of allergies and atopy related to stabilized Treg differentiation, and Thongaram discloses formula-fed infants lack exposure to the health-promoting oligosaccharides and microbes found in human milk, and therefore emphasizes the importance of the delivery of HMOs and probiotic bacteria in infant formula.
One of ordinary skill in the art would have had a reasonable expectation of success because the reference application, Shroven and Thongaram relate to compositions of HMOs, and Thongaram and Melnik relate to the benefits of probiotic exposure to developing infants.
Regarding instant claim 13, Shroven discloses the method can be applied to HMO blends that include a mixture of two or more HMOs that include 3’-SL and 6’-SL which are sialylated HMOs, and 2’-FL [p 98, lines 14-20], wherein 2’-FL is a neutral HMO as evidenced by the instant specification [p 13, lines 11-18].
Regarding instant claim 14, Shroven discloses the method can be applied to HMO blends that include a mixture of two or more HMOs that include 2’-FL [p 8, lines 14-20], wherein 2’-FL is a neutral HMO as evidenced by the instant specification [p 13, lines 11-18]).
Regarding instant claim 15, Shroven discloses the method can be applied to HMO blends that include a mixture of two or more HMOs that include 3’-SL and 6’-SL [p 8, lines 14-20] which are sialylated HMOs.
Regarding instant claims 17 and 23, Shroven discloses the use of the amorphous HMO powder obtained by the disclosed method for making nutritional formulations intended for use with infants [p 10, lines 14-15] which encompasses the limitation of an infant formula recited in claim 17.
Regarding instant claims 18-22, Shroven discloses the method discussed in the rejection of claim 12 above, comprising providing an HMO in an aqueous solution, wherein the HMO is at a concentration up to 60 wt %, and removing substantially all of the water via spray-drying, particularly at least about 95% of the water to provide the HMO precursor blend with a higher glass temperature of at least 40 °C [p 3, final para to p 5, first para], wherein a glass temperature is a function of water content, and a glass temperature of at least 40 °C is associated with a water content of 4-6% or less [p 9, para 4]. Therefore Shroven discloses the removal of at least 95% of the water of the aqueous solution of HMO to achieve increasingly high glass temperatures associated with such water content, and therefore the resulting spray-dried HMO is understood to contain 5% water or less.
While Shroven does not explicitly disclose the spray-dried powder of at least 85% 3’-SL and/or 6’-SL (as recited in the claim 18), at least 90% 3’-SL and/or 6’-SL (as recited in the instant claim 19), at least 93% 3’-SL and/or 6’-SL (as recited in the instant claim 20), at least 95% 3’-SL and/or 6’-SL (as recited in the instant claim 21) and at least 98% 3’-SL and/or 6’-SL (as recited in the instant claim 22), one of ordinary skill in the art would reasonably conclude that carrying out the method of Shroven and removing substantially all of the water from an aqueous solution comprising an HMO would increase the wt % of said HMO to the recited wt % of claims 18-22.
Additionally, MPEP 2144.05.II.A states 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. As Shroven discloses a spray dried mixture of HMOs with substantially all water removed, and provides a motivation for increasing concentrations of said HMOs in the mixture in order to produce quantities of HMOs to discover their uses in nutritional and therapeutic formulations, it would have been obvious to utilize the method of Shroven to increase the concentrations of HMOs to the ranges recited in the instant claims 18-22 through routine optimization.
Regarding instant claim 24, Shroven discloses the spray-drying of 6’-SL that is the sodium salt of the benzyl glycoside of 6’-SL synthesized according to WO 2011/100979 [p 14, “Example 3”], wherein the method of WO 2011/100979 is a chemical synthesis method [see Figueroa, p 3, “Summary of Invention”]. As the 6’-SL of Shroven is the result of chemical synthesis, the spray-dried mixture of Shroven is considered free of nucleic acid molecules derived from genetically-engineered microorganisms.
Additionally, Thongaram relates to human-associated bifidobacterial and lactobacilli, which are considered to be naturally-occurring bacteria [title], the combined spray-dried mixture of Shroven, Thongaram and Melnik is considered free of genetically-engineered microorganisms, and therefore also free of nucleic acid molecules derived from genetically-engineered microorganisms.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
D. Claims 12-15 and 17-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-32 of copending Application No. 18/417034 (filed 01/19/2024; herein “reference application”) in view of Shroven, Thongaram, Melnik and evidentiary reference Figueroa.
The instant rejection is maintained from the previous Office Action and any newly recited portions are necessitated by claim amendment.
Regarding instant claim 12, claim 30 of the reference application recites a spray-dried powder consisting essentially of sialylated oligosaccharide with a purity >80% by dry-weight and possessing less than 10% water by weight, wherein the oligosaccharide has been produced by microbial fermentation, and wherein the powder is capable of being formulated into a nutritional composition such as infant formula. Claim 31 of the reference application recites the oligosaccharide is 3’-SL, 6’-SL or a mixture of the two. Claim 32 of the reference application recites the powder consists of a mixture of 3’-SL, 6’-SL and one or more neutral HMOs such as 2’-FL, LNT and LNnT.
The claims of the reference application do not recite the powder comprises less than or equal to 5 %-wt water, probiotics and tyndalized probiotic bacteria.
Shroven discusses enhancing the stability and purity and increasing the bioavailability of human milk oligosaccharides or precursor [title]. Shroven describes the motivation in the field for making industrial quantities of different HMOs to be for the discovery of their uses in nutritional and therapeutic formulations [p 2, para 1].
Regarding instant claim 12 and the limitation of the spray-dried composition comprising at least 80%-wt 3’-SL and/or 6’-SL and less or equal to 5%-wt water, Shroven describes methods of providing an HMO in an aqueous solution, wherein the HMO is at a concentration up to 60 wt %, and removing substantially all of the water via spray-drying, particularly at least about 95% of the water to provide the HMO precursor blend with a higher glass temperature of at least 40 °C [p 3, final para to p 5, first para], wherein a glass temperature is a function of water content, and a glass temperature of at least 40 °C is associated with a water content of 4-6% or less [p 9, para 4]. Therefore Shroven discloses the removal of at least 95% of the water of the aqueous solution of HMO to achieve increasingly high glass temperatures associated with such water content, and therefore the resulting spray-dried HMO is understood to contain 5% water or less as recited in the claim.
Shroven further discloses the HMO can be any of a group consisting of 3'-SL and 6'-SL [p 8, lines 3-8]. While Shroven does not explicitly disclose the spray-dried powder of at least 80% 3’-SL and/or 6’-SL as recited in the claim 12, one of ordinary skill in the art would reasonably conclude that carrying out the method of Shroven and removing substantially all of the water from an aqueous solution comprising an HMO would increase the wt % of said HMO to the recited wt % of the claim. Put another way, carrying out the method of Shroven on an aqueous mixture of 60 wt-% HMO to remove substantially all of the water will reduce the total weight of the mixture, thereby increasing wt-% of the HMO to the claimed range, as one of skill in the art would be motivated to remove increasing amounts of water in order to increase the glass temperature of the powder, in order to produce quantities of HMOs to discover their uses in nutritional and therapeutic formulations as disclosed by Shroven.
Thongaram relates to HMO consumption by probiotic and human-associated bifidobacterial and lactobacilli [title], and discusses that human milk contains HMOs as well as bifidobacterial and lactobacilli that readily colonize the infant GI tract [p 7825, col 2, para 2].
Regarding instant claim 12, Thongaram discloses that formula-fed infants lack exposure to the health-promoting oligosaccharides and microbes found in human milk, and therefore emphasizes the importance of the delivery of HMOs and probiotic bacteria in infant formula [p 7825, col 2, para 2].
Melnik relates to milk and the postnatal imprinting system stabilizing regulatory T cell (Treg) differentiation [title], and discusses that breastfeeding has protective effects or the development of allergies and atopy, and identifies the biological role of milk controlling stabilized Treg differentiation [abstract]. While Melnik refers to cow’s milk, the findings of Melnik are related to the immunological benefits of children who consume said milk throughout development [p 1, col 1, para 1].
Regarding instant claim 12, Melnik discloses that the heat-killed probiotic L. pentosus strain S-PT84 was able to exhibit anti-allergic effects through the modulation of Th1/Th2 balance and Treg induction, as well as that both live and heat-killed probiotic L. rhamnosus could induce the anti-inflammatory cytokine IL-10 [p 4, col 2, para 2], wherein heat-killed cultures are understood as tyndalized cultures according to the specification [p 17].
In view of Shroven, Thongaram and Melnik, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the reference application by lowering the water content as disclosed by Shroven and adding the probiotics of Thongaram and tyndalized probiotics of Melnik, to arrive at the claimed invention.
One of ordinary skill in the art would have been motivated to modify the claims of the reference application by lowering the water content because Shroven discloses such compositions with low water content display enhanced stability and HMO bioavailability.
One of ordinary skill in the art would have been motivated to modify the claims of the reference application by including the probiotics of Thongaram and Melnik, because Melnik discloses that breastfeeding has protective effects or the development of allergies and atopy related to stabilized Treg differentiation, and Thongaram discloses formula-fed infants lack exposure to the health-promoting oligosaccharides and microbes found in human milk, and therefore emphasizes the importance of the delivery of HMOs and probiotic bacteria in infant formula.
One of ordinary skill in the art would have had a reasonable expectation of success because the reference application, Shroven and Thongaram relate to compositions of HMOs, and Thongaram and Melnik relate to the benefits of probiotic exposure to developing infants.
Regarding instant claim 13, Shroven discloses the method can be applied to HMO blends that include a mixture of two or more HMOs that include 3’-SL and 6’-SL which are sialylated HMOs, and 2’-FL [p 98, lines 14-20], wherein 2’-FL is a neutral HMO as evidenced by the instant specification [p 13, lines 11-18].
Regarding instant claim 14, Shroven discloses the method can be applied to HMO blends that include a mixture of two or more HMOs that include 2’-FL [p 8, lines 14-20], wherein 2’-FL is a neutral HMO as evidenced by the instant specification [p 13, lines 11-18]).
Regarding instant claim 15, Shroven discloses the method can be applied to HMO blends that include a mixture of two or more HMOs that include 3’-SL and 6’-SL [p 8, lines 14-20] which are sialylated HMOs.
Regarding instant claims 17 and 23, Shroven discloses the use of the amorphous HMO powder obtained by the disclosed method for making nutritional formulations intended for use with infants [p 10, lines 14-15] which encompasses the limitation of an infant formula recited in claim 17.
Regarding instant claims 18-22, Shroven discloses the method discussed in the rejection of claim 12 above, comprising providing an HMO in an aqueous solution, wherein the HMO is at a concentration up to 60 wt %, and removing substantially all of the water via spray-drying, particularly at least about 95% of the water to provide the HMO precursor blend with a higher glass temperature of at least 40 °C [p 3, final para to p 5, first para], wherein a glass temperature is a function of water content, and a glass temperature of at least 40 °C is associated with a water content of 4-6% or less [p 9, para 4]. Therefore Shroven discloses the removal of at least 95% of the water of the aqueous solution of HMO to achieve increasingly high glass temperatures associated with such water content, and therefore the resulting spray-dried HMO is understood to contain 5% water or less.
While Shroven does not explicitly disclose the spray-dried powder of at least 85% 3’-SL and/or 6’-SL (as recited in the claim 18), at least 90% 3’-SL and/or 6’-SL (as recited in the instant claim 19), at least 93% 3’-SL and/or 6’-SL (as recited in the instant claim 20), at least 95% 3’-SL and/or 6’-SL (as recited in the instant claim 21) and at least 98% 3’-SL and/or 6’-SL (as recited in the instant claim 22), one of ordinary skill in the art would reasonably conclude that carrying out the method of Shroven and removing substantially all of the water from an aqueous solution comprising an HMO would increase the wt % of said HMO to the recited wt % of claims 18-22.
Additionally, MPEP 2144.05.II.A states 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. As Shroven discloses a spray dried mixture of HMOs with substantially all water removed, and provides a motivation for increasing concentrations of said HMOs in the mixture in order to produce quantities of HMOs to discover their uses in nutritional and therapeutic formulations, it would have been obvious to utilize the method of Shroven to increase the concentrations of HMOs to the ranges recited in the instant claims 18-22 through routine optimization.
Regarding instant claim 24, Shroven discloses the spray-drying of 6’-SL that is the sodium salt of the benzyl glycoside of 6’-SL synthesized according to WO 2011/100979 [p 14, “Example 3”], wherein the method of WO 2011/100979 is a chemical synthesis method [see Figueroa, p 3, “Summary of Invention”]. As the 6’-SL of Shroven is the result of chemical synthesis, the spray-dried mixture of Shroven is considered free of nucleic acid molecules derived from genetically-engineered microorganisms.
Additionally, Thongaram relates to human-associated bifidobacterial and lactobacilli, which are considered to be naturally-occurring bacteria [title], the combined spray-dried mixture of Shroven, Thongaram and Melnik is considered free of genetically-engineered microorganisms, and therefore also free of nucleic acid molecules derived from genetically-engineered microorganisms.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Remarks: Beginning on page 9 of Applicant’s response to the Non-Statutory Double Patenting rejections; Applicant requests the double patenting rejections be reconsidered and/or otherwise deferred until the present claims have been reconsidered and are otherwise considered to be in condition for allowance.
Applicant’s request is acknowledged and the rejections are maintained, and updated above to reflect the amendments to the instant claims.
Conclusion
Status of the Claims:
Claims 6-10, 12-15 and 17-24 are pending.
Claims 6-10 are withdrawn.
Claims 12-15 and 17-24 are rejected.
No claim is in condition for allowance.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH SPANGLER whose telephone number is (571)270-0314. The examiner can normally be reached M-F 7:30 am - 4:30 pm.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656