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 .
DETAILED ACTION
The amendment to the claims filed after non-final office action on November 6, 2025 is acknowledged. Claims 1-2, 15, 21 were amended and claims 1-26 are pending in the instant application. The restriction was deemed proper and made final previous office action.
The restriction was deemed proper and made FINAL previously. Claims 18-19 remain withdrawn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. Claims 1-17, 20-26 are examined on the merits of this office
action.
Withdrawn Rejections/Objections
The rejection of claims 2-9, 13-17, 20-25 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of amendment of the claims filed November 6, 2025.
The rejection of claims 1-17 and 20-26 are rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement (new matter) is withdrawn in view of amendment of the claims filed November 6, 2025.
The rejection of claim(s) 1-17 and 20-26 are rejected under 35 U.S.C. 103 as being unpatentable over Yanhong (CN104430899 A1,cited in Applicant’s IDS) as evidenced by Layman (Nutrition Reviews, Vol. 76, pages 444-460, 2018, see attached handout) in view of Jun (CN102524422 B, cited in Applicant’s IDS with translation) as evidenced by Whey Protein 101 (Whey Protein 101: the Ultimate Beginners Guide, 2018, cited previously), Zhiyong (Dairy Industry, 2017, pages 1-13, cited in Applicant’s IDS filed May 20, 2024) and GNPD (Mintel, 2015, stage 1 baby formula, cited in Applicant’s IDS) is withdrawn in view of amendment of the claims filed November 6, 2025 to require purified lactoferrin.
.
New Rejections
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-17 and 20-26 are rejected under 35 U.S.C. 103 as being unpatentable over Yanhong (CN104430899 A1,cited in Applicant’s IDS) as evidenced by Layman (Nutrition Reviews, Vol. 76, pages 444-460, 2018, see attached handout) in view of Jun (CN102524422 B, cited in Applicant’s IDS with translation) as evidenced by Whey Protein 101 (Whey Protein 101: the Ultimate Beginners Guide, 2018, cited previously), Zhiyong (Dairy Industry, 2017, pages 1-13, cited in Applicant’s IDS filed May 20, 2024), GNPD (Mintel, 2015, stage 1 baby formula, cited in Applicant’s IDS), Drummond (“Drummond food Science Advisory, 2016, GRAS notice) and Okonogi (US4791193 A).
Yanhong teaches an infant formula comprising raw milk at 57-62% of the formulation (which milk is 3.3% protein as evidenced by Layman (see figure 1), thus the raw milk protein would be 2.046 % of the formulation, 3.3% of 62% would be 2.046%); hydrolyzed whey at 1.7-1.87% of the formulation and 1.6% to 2.2% of alpha-lactalbumin in the formulation. Yanhong teaches wherein the hydrolyzed protein is hydrolyzed whey Lacprodan 3071 (see claim 2). Yanyong teaches that the raw milk is Cow’s milk and whole milk (see bottom of page 7 of translation). As evidenced by Layman, the lactoferrin is present in Cows and Human milk and is 0.3% of total protein in cow’s milk (see page 445, left hand column, figure 1). If one assumes 62% (based on the range in instant claim 1 of Yanhong) of the formulation was milk (the raw milk protein would be 2.046 % of the formulation), alpha-lactalbumin would be 1.6-2.2% and WPH would be 1.7-1.87%. The total percentage of the formulation with WPH, alpha-lactalbumin and milk would be 5.346 (1.6+1.7+2.046) and WPH would be 29%(1.6/5.346) of the protein; lactalbumin would be about 31%(1.7/5.346) of the protein. Yanhong teaches isolated lactalbumin powder was purchased form a food trade company thus meeting the limitations of the formulation comprising lactalbumin isolate (see page 8 of translation, line 9). Yanhong teaches adding the isolate into the milk after sterilization of the milk (see section (2), page 4) and then spray drying. Yanhong teaches adding the lactalbumin isolate into the milk after sterilization of the milk (see section (2), page 4) and then spray drying.
Yanhong is silent to the range of alpha-lactalbumin in an amount of about 5% to about 25% and purified lactoferrin from using weakly acidic cationic exchange (separate from the amount in milk) that is about 0.5-6%.
However, Jun discloses an infant formula milk powder comprising the digestion aiding protein alpha-lactalbumin (referred to as ALA throughout Jun) and the immunoprotective protein lactoferrin (see claim 1). Jun teaches various infant formulations comprising different acceptable amounts of ALA and lactoferrin (see Embodiments 1-10).
Example 5 of Jun discloses a composition comprising 2.16 grams of alpha-lactalbumin, 0.18 grams of lactoferrin (a ratio of 12:1 and a total amount of 2.34 grams); 13 grams of skim milk powder (which is 0.4244 grams of protein given there are 8 grams of protein per 1 cup (245 grams) of skimmed milk); 10 grams of whey powder (of which whey powder is approximately 70-90% protein as evidenced by “Whey protein 101”, see attached handout, page 3, and thus 70% would have 7 grams of protein); 5 grams of whey protein thus resulting in a total protein amount of 14.7644 grams of protein. The percent amount of alpha lactalbumin protein in the protein component of the formulation would be 2.16/14.7644 which is 14.6% thus falling within the range of 5-25% and 4-20% of instant claims 1-2. The lactoferrin concentration would be 1.2%.
Jun teaches “The infant formula milk powder contains a specific amount of alpha-lactalbumin and lactoferrin and is close to breast milk. One small step is made in the progress of breast milk conversion of the infant formula milk powder.” Jun further teaches by supplementing with immune supporting proteins which are close to the breast milk, this will improve immunity of infants (see abstract). Thus, the goal of Jun was to create a formula that it is immune supporting and more closely mimicking of breast milk. Jun teaches mixing all of the components except for ALA and lactoferrin and then spray drying and then adding ALA and lactoferrin (see top of page 5, paragraphs 0079-0080). Thus, the ALA and lactoferrin are separate isolated components that are blended into the other components after spray drying.
Zhiyong teaches alpha lactalbumin accounts for 27% of protein in breast milk and only 4% in cow’s milk, thus the need to supplement in infant formula with cow’s milk (see page 3, second paragraph). Zhiyong teaches lactoferrin in breast milk (see table 4). Zhiyong teaches that multiple antibacterial clinical trials of lactoferrin in infants show that adding 1 mg/ml of bovine lactoferrin (isolated exogenous lactoferrin) to infant formula leads to increase in both bifidobacterial number and ferrin content (See page 5, last two paragraphs). Lactoferrin can inhibit viruses and reduce incidence of diarrhea (see page 5, last two paragraphs).
GNPD (Stage 1 Baby Formula, Mintel, cited in Applicant’s IDS, published 2015) teaches an infant formula comprising hydrolyzed whey, skimmed milk powder, lactose, vegetable oils, lactoferrin (50 mg), alpha-lactalbumin (1800 mg) and total protein of 11 grams. Thus, the amount of lactoferrin is 0.45% (which meets the limitations of about 0.5%) and the amount of alpha-lactalbumin is 16.36% meeting the limitations of 5-25% alpha lactalbumin.
Drummond teaches of milk derived bovine lactoferrin for use in formulas including infant formulas (see Tables 2-5). Drummond teaches wherein the lactoferrin is greater than or equal to 95% purity (see page 34, tables 2-5) and wherein part of the lactoferrin is iron saturated and some not iron saturated (see Table 2, page 34, also Table 2-3, both iron saturated and not saturated forms present). Drummond teaches that the Bovine milk derived lactoferrin is considered to be safe for the intended use of infant formula (see page 13). Drummond additionally teaches that the lactoferrin is obtained from milk filtrate being passed over an ion exchange column containing Sepharose (see page 26 and also page 27, “Materials and processing Aids”, Also Table 2-4).
Okonogi teaches methods of purifying bovine lactoferrin from raw milk using weakly acidic cationic exchanger (see abstract).
It would have been obvious before the effective filing date of the claimed invention to include at least 0.5 % (including 1%) of purified lactoferrin (independent from what is found in the milk naturally) in the infant formulations of Yanhong. One of ordinary skill in the art would have been motivated to do so to mimic breast milk, provide immune supporting proteins such as purified lactoferrin (which is safe and pure as taught by Drummond) with the expectation of improving immunity or to provide immune support (see abstract). There is a reasonable expectation of success given that purified lactoferrin (in combination with WPH and alpha lactalbumin) in infant formula is beneficial in being a nutritional source, immune supporting, more closely mimics breast milk and safe for use.
Furthermore, regarding use of purified lactoferrin, one of ordinary skill in the art would have been motivated to use purified lactoferrin in infant formula given purified lactoferrin inherently contains fewer non lactoferrin milk components and residual impurities, which is a routine and expected outcome of purification. The use of purified lactoferrin therefore represents a conventional optimization to ensure consistent composition and quality of a known ingredient in infant nutritional products, with a reasonable expectation of success.
Regarding the newly added limitation of “obtained from raw milk material using a weakly acidic cation exchanger” in instant claims 1 and 15, this additional product by process limitation does not distinguish the claimed product from the prior art. As set out in Drummond, bovine lactoferrin is isolated from raw milk and skim milk using ion exchange chromatography, specifically using Sepharose Big Beads as the ion exchange resin (see Drummond, Table 2-4 and manufacturing description). The bound lactoferrin is eluted with sodium chloride, desalted by ultrafiltration, and spray dried to form purified lactoferrin dry particles.
Under product-by-process claim interpretation (see MPEP 2113), patentability is based on the product itself, not the recited process steps. Here, the prior art product is the same or indistinguishable from the claimed product, the product by process limitation does not impart patentable distinction even if the process were different.
Nevertheless, Okonogi teaches methods of purifying bovine lactoferrin from raw milk using weakly acidic cationic exchanger (see abstract).
It would have been obvious to a person of ordinary skill in the art to purify lactoferrin using a weakly acidic cation-exchange process because Okonogi expressly teaches this purification method for lactoferrin from raw milk. Applying Okonogi’s known purification technique to the lactoferrin Yanhong in view of Jun, Zhiyong, GNPD, Drummond constitutes a routine substitution of equivalent purification methods that does not impart patentable distinction to the resulting product under product-by-process principles (MPEP § 2113).
Regarding claims 1-2, 8-9, 11-15, 17, 21, the amount of Whey protein hydrolysate, lactoferrin and alpha-lactalbumin and milk protein are considered result effective variables and one of ordinary skill in the art would have optimized the amount of all components in the formula (within the amounts taught by Yanhong, Jun, Zhiyong and GNPD) to most closely mimic breast milk and/or to provide optimal immune support and nutrition to the infant (see MPEP 2144.05 (A)). Furthermore, MPEP 2144.05 states “In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)”.
Regarding claims 3-7 and 22-25, Yanhong teaches wherein the raw milk is whole milk and cow’s milk (see bottom of pages 4 and 7, raw milk (full fat) or skimmed, which is no fat). It would have been obvious to try full fat, skimmed milk or low fat milk based on the needs of infant nutrition and one of ordinary skill art would have recognized that any one of those milk options would be effective for the purpose of formula nutrition.
Regarding claims 9 and 15, the ratio of WPH/lactoferrin by weight (not protein) would be about 7:1 based on the lactoferrin found in the milk (i.e.1.87% WPH taught by Yanhong and .3% in bovine milk of lactoferrin as evidenced by Layman). Furthermore, the combined teachings of Yanhong and Jun would render obvious the ratio of WPH and lactoferrin found in instant claim 9 (i.e. 1.87% WPH of Yanhong and 0.5% of lactoferrin, ratio of about 3:1). Furthermore, Jun teaches a ratio of alpha-lactalbumin to lactoferrin of 2:1 (see claim 6). Nevertheless, it would have been obvious to optimize the amount of both components in the formula as stated above to achieve optimal therapeutic effectiveness in the infant formula. In particular, to achieve a formula that most closely mimics human breast milk, contains optimal protein supplementation and antibacterial activities (lactoferrin) all of which contribute to growth and development in infants.
Regarding claims 10, 16 and 26, Yanhong teaches the formulation comprises fat and lactose (see claim 1) and where the fat is vegetable oil (see page 4, third paragraph, page 5, second paragraph.
Regarding claims 11-12, as stated above, Yanhong teaches WPH at 29% of the total protein. If one assumes 62% (based on the range in instant claim 1 of Yanhong) of the formulation was milk (the raw milk protein would be 2.046 % of the formulation), alpha-lactalbumin would be 1.6-2.2% and WPH would be 1.7-1.87%. The total percentage of the formulation with WPH, alpha-lactalbumin and milk would be 5.346 (1.6+1.7+2.046) and WPH would be 29%(1.6/5.346) of the protein; lactalbumin would be about 31%(1.7/5.346) of the protein. Regarding claims 13-14, Jun and GNPD all teach an alpha lactalbumin concentration in the range of 14-20% of the protein. As stated above, it would have been obvious to optimize the amount of alpha lactalbumin protein within the formulation based on the amounts known for the same purpose in the prior art to most closely mimic breast milk and to provide optimal immune support and nutrition to the infant.
Regarding claims 10, 16 and 26, Yanhong teaches including galactooligosaccharide (see claim 3).
Regarding claim 17, Yanhong teaches the formulation comprising milk in the range of 35-38% (1.881 or 2.046/total protein (say 5.346 total protein)). Regarding the amounts of that milk contributes to the protein found in instant clams 2, 21, it would have been obvious to optimize the amount of milk in the formulation to achieve the optimal amount of protein to be delivered to the infant. The amount of milk provided protein is a result effective variable and it would be obvious to optimize the amount dependent on the needs of the infant desired nutrition.
Regarding claim 20, Yanyong teaches that the raw milk is Cow’s milk and whole milk (see bottom of page 7 of translation).
Response to Applicant’s Arguments
Applicant argues “the prior art combination fails to teach or suggest alpha-lactalbumin, WPH and purified lactoferrin that is obtained from raw milk using weakly acidic cationic exchange”. While the combination of Yanhong, Jun, Zhiyong, and GNPD reference infant formula compositions comprising WPH and/or alpha-lactalbumin, none of these prior art references disclose the combination of whey protein hydrolysate, alpha-lactalbumin, milk protein, and purified lactoferrin, let alone purified obtained from raw milk material using a weakly acidic cationic exchanger. Yanhong makes no mention of using isolated lactoferrin, GNPD does not teach or suggest purifying lactoferrin. Even assuming, arguendo, that the Office has a reason to modify the prior art by purifying lactoferrin, none of the prior art references teach or suggest obtaining purified lactoferrin from raw milk material using a cationic exchanger under weakly acidic conditions. As noted at paragraph [088] of the originally filed specification, the purification process obtains "lactoferrin from raw milk material using a weakly acidic cationic exchanger, a washing step to remove nonabsorbed substances, and a desorbing step to obtain purified lactoferrin." As explained below, this process results in less iron saturation than naturally isolated lactoferrin. Exhibit 1 evidences that iron atoms bound to lactoferrin are "removed under acidic conditions." For example, at weakly acidic pH 5.0, about 75% of bound iron is retained. Id. Thus, using a cationic exchanger under weakly acidic conditions results in less iron content bound to the lactoferrin than naturally isolated lactoferrin. U.S. Patent No. 4,791,193 (which is incorporated by reference at paragraph [088]), explains the use of weakly acidic conditions for the cation-exchanger of the present invention to purify lactoferrin (col 5, lines 39-66) under weakly acidic conditions; these weakly acidic conditions have pH range of between 4.6 to 6.7 (see, e.g., col 3, lines 42-55; Table 1; and Examples 1-10 of the '193 Patent). As evidenced above, these conditions lead to purified lactoferrin that have less iron saturation than lactoferrin found in bovine milk. There is no reason why one of ordinary skill in the art would go through the added time and expense of purifying lactoferrin in this manner over existing lactoferrin found in milk or isolated in some other manner absent impermissible hindsight.
Applicant’s arguments have been fully considered but not found persuasive. The rejection is based on the combination of references. It is not necessary that any single reference disclose all elements of the claimed invention (see MPEP 2145IV). Yanhong teaches infant formula comprising milk and hydrolyzed when protein. Jun teaches supplementation of infant formula with alpha-lactalbumin and lactoferrin. Zhiyong teaches varying concentrations of alpha lactalbumin and lactoferrin in breast milk an infant formulas. GNPD teaches an infant formula comprising hydrolyzed whey, skimmed milk powder, lactose, vegetable oils, lactoferrin (50 mg), alpha-lactalbumin (1800 mg) and total protein of 11 grams.
Drummond teaches purified bovine lactoferrin suitable for infant formula. Okonogi teaches purification of lactoferrin from raw milk using a weakly acidic cation exchanger.
It would have been obvious before the effective filing date of the claimed invention to include at least 0.5 % (including 1%) of purified lactoferrin (independent from what is found in the milk naturally) in the infant formulations of Yanhong. One of ordinary skill in the art would have been motivated to do so to mimic breast milk, provide immune supporting proteins such as lactoferrin (which is safe and pure as taught by Drummond) with the expectation of improving immunity or to provide immune support (see abstract). There is a reasonable expectation of success given that purified lactoferrin (in combination with WPH and alpha lactalbumin) in infant formula is beneficial in being immune supporting, more closely mimics breast milk and safe for use.
Furthermore, regarding use of purified lactoferrin, one of ordinary skill in the art would have been motivated to use purified lactoferrin in infant formula given purified lactoferrin inherently contains fewer non lactoferrin milk components and residual impurities, which is a routine and expected outcome of purification. The use of purified lactoferrin therefore represents a conventional optimization to ensure consistent composition and quality of a known ingredient in infant nutritional products, with a reasonable expectation of success.
With respect to the limitation “purified lactoferrin obtained from raw milk material using a weakly acidic cationic exchanger”, this is a product by process limitation. Under MPEP 2113, patentability is based on the product itself, not the recited process steps. Applicant has not shown that the claimed lactoferrin is structurally different from the purified of the prior art. The claims do not recite any limitation regarding iron saturation or any structural property resulting from the purification conditions. Unclaimed properties cannot confer patentable distinction.
Nevertheless, Okonogi teaches methods of purifying bovine lactoferrin from raw milk using weakly acidic cationic exchanger (see abstract).
It would have been obvious to a person of ordinary skill in the art to purify lactoferrin using a weakly acidic cation-exchange process because Okonogi expressly teaches this purification method for lactoferrin from raw milk. Applying Okonogi’s known purification technique to the lactoferrin Yanhong in view of Jun, Zhiyong, GNPD, Drummond constitutes a routine substitution of equivalent purification methods that does not impart patentable distinction to the resulting product under product-by-process principles (MPEP § 2113).
Applicant argues that “One of ordinary skill in the art would have been led away from using purified II. lactoferrin and modifying the amounts of protein in the formulation of Yanhong as proposed by the Office because Yanhong teaches away from modulating the concentrations and because the claimed purified lactoferrin has less iron saturation, which is less resistant to thermal denaturation and proteolysis. Here, Yanhong specifically notes that the technical problem to be solved was developing a muting sensitive infant formula that is "difficult" in "proportioning" when "taking into account each nutritional ingredient," "dissolution velocity," "reconstituting" with "small particles," and the "bitter defect of mouthfeel." (Yanhong, "Background Technology"). The resulting formula "is balanced with each nutritional ingredient" and "takes into account [sub-sensitivity]" and the "dissolution velocity is fast, easily reconstitute no small particles, and taste flavor is pleasant." Id. In fact, Yanhong notes that "a large amount of experimental exploring and practical proof repeatedly" to achieve the amounts of infant formula components. Id. In other words, Yanhong warns that modifying proportions destroys the principle of operation. As noted by the Office, Yanhong controls lactoferrin using specific amounts of "Lacprodan 3071." The range of Lacprodan® is incredibly precise: "The content of described partially hydrolysed protein is 1.70% ~ 1.87%, is preferably 1.72% ~ 1.86%, is more preferably 1.72% ~ 1.78%, and described percentage is the mass percent accounting for raw material gross mass." (Yanhong, claim 2 and page 2). Therefore, proportions of lactoferrin are specifically controlled to avoid the negative side effects discussed above, which contradicts the Office's assertion that Yanhong's "proportions of each components/supplements are in fact, results effective variable and it is obvious to optimize to achieve optimal taste and dissolution." (NFOA, page 16). Yanhong's negative side effects "criticize, discredit, or otherwise discourage" modulation of concentrations, which are precisely what the Office alleges is required to determine a teaching away. Yanhong explicitly teaches away from modifying the proportions of Yanhong's ingredients, including by adding the amounts of lactoferrin of Jun and Zhiyong, because this leads to poor product taste, poor dissolution velocity when reconstituting, and an accumulation of small particles. (Yanhong, "Background Technology"). In other words, the Office's proposed modification of Yanhong "to include at least 1% of lactoferrin (independent from what is found in the milk naturally) in the infant formulations of Yanhong" is specifically taught away by Yanhong and destroys the principle of operation of Yanhong since this leads to destroying the unique properties of taste, dissolution, small particle phenomenon that Yanhong was able to overcome based on the specific proportions of the ingredients.
Applicant’s arguments have been fully considered but not found persuasive. A reference teaches away only when it criticizes, discredits, or otherwise discourages the claimed solution. Mere disclosure of preferred or optimized ranges does not constitute teaching away (see MPEP 2145 D(1)). Yanhong discloses preferred concentration ranges to achieve desirable taste and dissolution properties but does not criticize or discourage the addition or adjustment of immune-supporting proteins such as lactoferrin. Rather Yanhong is directed to improving infant formula performance through controlled formulation. The disclosure of preferred proportions does not rise to the level of a clear discouragement from routine optimization. Furthermore, Jun and Zhiyong expressly teach supplementation of infant formula with lactoferrin to more closely mimic breast milk and improve immune support. Where references address the same filed and objective, it is proper to combine them even if one reference expresses preferences. The alleged concerns regarding taste or dissolution reflect predictable formulation tradeoffs and do not amount to a teaching away. Adjusting concentrations of known milk proteins in infant formula is a result effective variable and would have been within the routine skill of the art.
With respect to iron saturation and stability, the claims do no recite any limitations regarding iron content, stability, or resistance to denaturation. Unclaimed properties cannot confer patentability. Moreover, Okonogi teaches weakly acidic cation exchange purification of lactoferrin and Drummond teaches purified bovine lactoferrin suitable for infant formula use. The substitution of a known purification technique does not destroy the principle of operation of Yanhong. Accordingly, Applicant has not established that the prior art teaches away from the proposed combination, and the rejection is maintained.
Applicant argues “Moreover, a person of ordinary skill in the art would have been led away from an infant formula comprising purified lactoferrin obtained under weakly acidic conditions as recited in the claims. Exhibit 3 evidences that native isolated bovine lactoferrin has approximately 15-20% of iron saturation. 2 In contrast, as evidenced above, the purified lactoferrin of the claimed infant formula is more apo-lactoferrin ("apo-Lf") (i.e., less iron saturated) than naturally isolated lactoferrin, which is more holo-lactoferrin ("holo-Lf") due to the weakly acidic conditions for the cationic exchanger used during purification. Exhibit 2 evidences that the binding of iron by lactoferrin results in a change in its molecular conformation.³ In particular, when iron ions enter into the open interdomain cleft in each lobe of the lactoferrin, "the domains close over the iron atom resulting in a more compact structure. Thus, holo-Lf being more compact than the apo-Lf, is more resistant to thermal denaturation and proteolysis." Accordingly, it was well known prior to the effective filing date of the claimed invention that holo-Lfis a more stable form of lactoferrin because it is more resistant to thermal denaturation and proteolysis. Therefore, a person of ordinary skill in the art would choose lactoferrin with more iron saturation (i.e., holo-Lf) rather than the purified lactoferrin of the present invention that has less iron saturation. Given that holo-Lf is more resistant to thermal denaturation and proteolysis, a person of ordinary skill in the art would therefore have been led away from using a highly purified lactoferrin obtained using a weakly acidic cationic exchanger that is more apo-Lf than native bovine lactoferrin with a higher iron saturation because it is not as susceptible to thermal denaturation and proteolysis. Proceeding to use a purified bovine lactoferrin that is more apo-Lf would be contrary to the accepted wisdom to use lactoferrin with higher iron saturation such as native isolated bovine lactoferrin or the purified lactoferrin as taught by Drummond that is more holo-Lf because holo-LF is more stable. The fact the claimed invention proceeds with using a less table form lactoferrin is further evidence of nonobviousness.
Applicant’s arguments have been fully considered but not found persuasive. First, the claims do no recite any limitation regarding iron saturation, apo- or holo-lactoferrin content, thermal stability, proteolytic resistance, or any structural characteristic relating to iron binding. The claims recite only “purified lactoferrin obtained from raw milk material using a weakly acidic cation exchanger”. Under product by process principles (MPEP 2113), patentability is based on the product itself, no the recite process steps. Applicant has not demonstrated that the claimed lactoferrin is structurally distinct from the purified bovine lactoferrin taught in Drummond. Unclaimed properties cannot confer patentable distinction. Second, Okonogi teaches purification of bovine lactoferrin from raw milk using weakly acidic cationic exchange chromatography. Thus, the purification method recite in the claims was known in the art. The substitution of one known ion exchange purification technique for another represents routine selection of an established method and does not render the resulting infant formula nonobvious. Lastly, Applicant has not shown that the prior art criticizes, discredits or otherwise discourages the use of purified lactoferrin obtained under weakly acidic conditions. The alleged preference for higher iron saturation reflects a potential formulation consideration, not a clear teaching away from the claimed purification method. A reference teaches away only when it clearly discourages the claimed solution. Mere disclosure of advantages of an alternative form does not rise to the level of teaching away.
Applicant argues that the office improperly disregarded the evidence of unexpected results by failing to recognize synergy when the claimed components are combined. Here, as demonstrated above, the purified lactoferrin of the composition recited in the claims has a lower iron saturation than isolated/free lactoferrin of native bovine lactoferrin. Consequently, it would be expected to be less stable since it is less resistant to gastrointestinal digestion. However, the claimed combination surprisingly prevents this phenomenon from occurring based on the unexpected protective effect of the combination with WPH and alpha- lactalbumin. Applicant previously presented multiple Rule 132 Declarations based on the data in Rulan Jiang, et al., "Evaluation of Bioactivities of the Bovine Milk Lactoferrin-Osteopontin Complex in Infant Formulas," J. AGRIC. FOOD CHEM. 2020, 68, 6104-6111 (May 20, 2020), which is presented again here for the Office's convenience as Exhibit 4. In particular, Applicant discovered synergism based on an improved bioactivity of lactoferrin that is potentiated by WPH and alpha-lactalbumin that protect lactoferrin from digestion, resulting in significant improvement in the gut of infants when the protein components WPH, alpha-lactalbumin, and lactoferrin are combined and at different protein levels. See Declarations of Drs. Devon Kuehn and Bo Lonnerdal filed on 21 March 2021. Thus, synergy based on the claimed combination occurs across different protein levels, which means synergy occurs regardless of concentration. As a result, the claims are commensurate in scope with the data presented because synergism is based on the inventive contribution of the combination of the claimed components themselves (i.e., the protective effect of WPH and alpha-lactalbumin) rather than a particular concentration range. The Office does not dispute the evidence of synergism but rather blatantly ignores this evidence. The Office has provided no basis to question Applicant's comparative data and assertion that the demonstrated results were unexpected. Instead, The Office relies on references that are not relevant to the claimed invention. Specifically, the Office alleges that the effect discovered by Applicant is unexpected based on the fact that lactoferrin and osteopontin may form a complex as evidenced by Jiang (or "Liu"). Whether lactoferrin forms a complex with osteopontin has nothing to do with the protective effect of WPH and alpha-lactalbumin. Even if everything cited in this reference were true, it has no bearing on the effect on the combination of lactoferrin, WPH, and alpha-lactalbumin. Moreover, the Office's reliance on GNPD is also irrelevant given that purified lactoferrin, including specifically apo-lactoferrin as result of lactoferrin obtained under weakly acidic conditions is neither taught nor suggested by GNPD or the other cited references of record. It would be impossible to determine whether WPH and alpha-lactalbumin have a protective effect on purified lactoferrin absent experimentation. The office has not provided evidence to rebut Applicant’s assertions of unexpected results and should accept statement at face value. Moreover, the Office's allegation that the evidence does "not provide amounts" of WPH, lactoferrin or alpha-lactalbumin is clearly not supported by the facts. First, independent claim 7 does not recite any specific amounts lactoferrin, WPH, and alpha-lactalbumin.
Applicants arguments have been fully considered but not found persuasive. Applicants argument relies on the assertion that independent claim 7 does not recite amounts. Claim 7 is not an independent claim. The independent claims presently pending do recite concentrations, and therefore Applicants commensurateness analysis is based on in accurate characterization of the claims.
The Jiang study (2020) and associated declarations evaluate protein blends under specific in vitro digestion conditions and attribute the observed effects to protein protein interactions with formula matrix. The evidence does not isolate the purification method or iron saturation states as the causal variable. The study does not compare purified lactoferrins. Accordingly, the asserted improvement lacks a demonstrated nexus to the claimed purification limitation. Second, although several ratios were tested, the experiments were conducted using defined blends at controlled concentrations. The claims encompass broad ranges and are not limited to the specific ratios or conditions evaluated. Evidence based on selected embodiments does not establish that the compositions within the claimed scope would exhibit the asserted protective effects. Therefore, the showing is not commensurate in scope with the breadth of the claims. Last, the office is not required to accept conclusory assertions of unexpected results at face value (see MPEP 716.01(C)). Where the evidence does not establish a nexus to the claimed features or does not reasonably support the full scope of the claims, it is insufficient to overcome a prima facie case of obviousness. However, the closest prior art already teaches formulas comprising the combination of lactoferrin, WPH, alpha-lactalbumin and milk protein. Demonstrating that proteins in combination influence digestion stability under in vitro conditions does not establish an unexpected property over the prior art compositions. Given the fact that formulations are known in the art to contain all of the claimed components, the question becomes whether or not the concentrations in the claims provide some sort of unexpected result or criticality of the claimed ranges. Applicants have not demonstrated that the claimed quantitative limitations yield such a critical or unexpected result. Therefore, the evidence does not rebut the prima facie case of obviousness.
Applicant further argues “Moreover, the data from Exhibit 5 shows various protein ratios across the lactoferrin, WPH, and alpha-lactalbumin combination recited in the claims that were subject to in vitro digestion. For example, Table 1 of Exhibit 5 (reproduced below) details the composition of three blends of lactoferrin, alpha- lactalbumin, and WPH across multiple protein ratios ("three formula protein blends [three mixtures of LF & OPN, WPH. , and α-LA. ") in units of g/L (see Table 1). As can be seen in Table 1, the amounts of lactoferrin were modulated relative to constant amounts of alpha-lactalbumin and WPH to demonstrate that potentiation occurs across different protein levels. Id. The above concentration ratio variations demonstrate not only that the concentrations are present, but also that these ratios were varied to prove synergy was not limited to a particular concentration. To further illustrate this point, the evidence presented in Exhibit 4 explicitly mentions that "the protein level was not constant among all samples in the in vitro analysis " and that "the effect itself that is the determination of unexpected results. Thus, the data demonstrates that synergism is not limited to a particular concentration range, that synergism occurs across a range of protein levels, and that the claimed combination itself is what drives the significant improvement in purified lactoferrin stability. As another data point, FIG. 2 of the article clearly shows data comparing lactoferrin/LF&OPN alone versus the combination of WPH and alpha-lactalbumin ("Blends") demonstrated as dark regions on the Western blot demonstrating regions that were not digested (reproduced below): As explained in the Declaration of Dr. Kuehn, the claimed combination of WPH, alpha- lactalbumin, and lactoferrin ("Blends") synergistically enhances lactoferrin based on a protective effect and this can be seen in FIG. 2: "An unexpected result of the study was that peptides and proteins in WPH and alpha-lactalbumin appear to protect lactoferrin from in vitro digestion, potentiating its bioactivity. This result follows from Figure 2 on page 6016 of the publication." (The declaration, paragraph 17). The Office does not dispute the above data or that there is a nexus between the combination of components and the resulting synergistic potentiating effect of the combination. Rather, the Office improperly disregards it because the Office is expecting unexpected results over a claimed range of the claimed composition. The Office's position is not grounded in law because Applicant need only present one common property of synergism for the protein combination: "Evidence that the compound or composition possesses superior and unexpected properties in one of a spectrum of common properties can be sufficient to rebut a prima facie case of obviousness." MPEP § 2145 citing In re Chupp, 816 F.2d at 646 (emphasis added). As noted above, none of the prior art references disclose a combination of WPH, alpha- lactalbumin isolate, and purified lactoferrin in any amount. The Office has not presented any rebuttal evidence to support its allegation that a specific concentration of each of the purified lactoferrin, WPH, and alpha-lactalbumin is critical or necessary for producing synergism between the claimed three components. To the contrary, Applicant has provided evidence showing that synergism occurs across different protein levels including three protein blends with different protein ratios, which means that synergism is based on the structural protective effect of WPH and alpha-lactalbumin rather than a particular concentration of components. The specific concentrations for each recited component are not critical. Thus, for the evidence of synergism to be commensurate in scope with the claims, the claims need to recite a formulation comprising the three components: purified lactoferrin, WPH, and alpha-lactalbumin, which is clearly recited in the independent claim(s). Accordingly, the claimed technology is commensurate in scope with the evidence demonstrating synergy.
Applicant’s arguments have been fully considered but not fond persuasive. Jiang (Exhibit 5) evaluates specific protein blends at defined concentrations under controlled in vitro conditions (Table 1). The claims are not limited to those specific ratios or conditions. Evidence based on selected experimental formulations does not reasonably establish that substantially all compositions within the scope of the claims would exhibit the asserted synergistic effect (see MPEP 716.02). Jiang (Exhibit 5) does not compare lactoferrin purified under the claimed weakly acidic conditions (or reduced iron saturation state) to prior art lactoferrin under otherwise identical formulation conditions. Accordingly, the evidence does not demonstrate that any observed protection is attributable to the claimed purification feature, rather than to routine protein-protein interactions known to occur in blended milk proteins.
Applicants argue that “Additional experiments of in vitro digestion without osteopontin was conducted to test each claimed component alone and in combination to demonstrate that the results are commensurate in scope with the claimed combination and confirm the synergistic protective effect. In response to the Office's allegation that Applicant's data shows a protective effect against lactoferrin and osteopontin (Lf-OPN) degradation but no data of lactoferrin alone and in combination with WPH and alpha-lactalbumin in combination (NFOA, pages 16-18), the following arguments are presented to further dispel the Office's assertion. While Applicant disagrees that osteopontin plays a role in the protective effect of WPH and alpha-lactalbumin, solely in an effort to advance prosecution, Applicant hereby provides additional evidence of synergy that addresses the Office's point of contention during the interview. In particular, the Office is respectfully directed to Exhibit 5, which tests in vitro digestion for each component alone (including lactoferrin) and in combination with WPH and alpha-lactalbumin.⁸ The lactoferrin ("Lf") used is Bioferrin® 1000, which is the same as Bioferrin® 2000 but with less iron saturation (see Table 1). Applicants conclude that As shown in figure 2D-F, both Lf and alpha-Lac are more resistant to in vitro digestion when complexed with each other or other proteins. As show in Figure 3, Lf alone and alpha Lac alone and each in complexes with other proteins were partly resistant to GI digestion, but they were protected when in protein blends (figures 3D-F). Moreover, as evidenced by Figures 2 D-F and 3 D-F of Exhibit 5, band 7 (i.e., blend 3 which corresponds with the claimed composition) had substantial improvement over bands 5 and 6 (i.e., blends 1 and 2) in terms of in vitro digestion when subjected to Native/SDS PAGE and when probed with anti-Lf and anti-α-Lac antibodies. Therefore, synergism was demonstrated by testing each component individually and in specific combinations and verify Applicant's assertion that synergism occurs when purified lactoferrin is combined with WPH and alpha-lactalbumin as recited in the claims resulting from the protective effect of the protein complex. Prior to the effective filing date of the claimed invention, the significant improvement in purified lactoferrin's resistance to gastrointestinal digestion based on the protective effect of WPH and alpha-lactalbumin was unknown, which the Office does not dispute. The substantially improved properties against digestion based on the claimed combination is "ipso facto unexpected" and "should suffice to establish unexpected results in the absence of evidence to the contrary."
Applicant’s arguments have been fully considered. Applicant relies on Exhibit 5 (Jiang et al, 2024) as additional evidence of synergistic protection of lactoferrin in the absence of osteopontin and asserts that the results are commensurate in scope and ipso facto unexpected under In re Soni.
Although Jiang evaluates lactoferrin alone and in specific blends (Blends 1–3), the experiments are limited to defined protein ratios under particular in vitro digestion conditions (pepsin at pH 4.0; pancreatin at pH 7.0; 30 minutes). The claims are not limited to these specific ratios, concentrations, digestion parameters, or experimental conditions. Evidence based on selected formulations does not reasonably establish that substantially all compositions within the scope of the claims would exhibit the asserted protective effect. See MPEP §716.02.
The data do not establish a nexus between the asserted unexpected results and the claimed purification feature (i.e., lactoferrin obtained under weakly acidic conditions or reduced iron saturation). While Applicant states that Bioferrin® 1000 has lower iron saturation, Jiang does not compare lactoferrin purified under the claimed conditions to prior art lactoferrin under otherwise identical formulation conditions. The observed protection is attributed in Jiang to protein complex formation among milk proteins. Such protein–protein interactions in blended milk systems would have been expected in the art and do not demonstrate that the purification method or iron saturation state confers a distinct, unexpected property.
Applicants further emphasize that Exhibit 5 includes testing of individual components alone.
However, testing components individually does not by itself establish unexpected results. The data show that each protein exhibits some digestion resistance and blends increased resistance. Applicants cite In Re Soni (54 F.3d (Fed Cir 1995), arguing that improved properties are “ipso facto unexpected”. In Soni, the claimed invention exhibited a dramatic and quantitively unexpected improvement, clearly beyond what the prior art would predict. Applicants reliance on In Re Soni is not found persuasive. The evidence does not compare the claimed purified lactoferrin to the closest prior art
lactoferrin compositions, nor does it isolate the alleged inventive feature (e.g. purification or iron saturation). Accordingly, the results are not “ipso facto unexpected” and do not demonstrate synergy or
rebut the prima facie case of obviousness.
Exhibit 5 does not establish synergism. Applicant characterizes the observed protection against in vitro digestion as “synergistic”. However, synergism requires a showing that the combined effect is greater than the expected additive effect of the individual components (see MPEP 716.02). Exhibit 5 shows lactoferrin alone exhibits some resistance to digestion, alpha lactalbumin alone exhibits some resistance to digestion, protein blends exhibit increased resistance relative to individual proteins. However, Applicant does not provide evidence of a synergistic effect. For all of the reasons stated above, the rejection is maintained.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
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