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
2. Applicants’ arguments and amendments filed on 12/18/2025, overcomes the rejections of record, however, the new grounds of rejection as set forth below are necessitated by applicants’ amendment and therefore, the following action is Final.
Any objections and/or rejections made in the previous action, and not repeated below, are hereby withdrawn.
Status of the application
3. Claims 1-7 are pending in this office action.
Claims 1-4, 6 have been amended.
Claims 1-7 have been rejected.
Claim Rejections - 35 USC § 112
4. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
5. Claims 1-7 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.
6. Claim 1 recites the phrase “controlled content of cobalamin”. In specification, it is noted that two fractions whose lactoferrin protein purity is >95% and whose vitamin B12 content is 5 μg/g protein and fraction whose lactoferrin protein purity is >90% and whose vitamin B12 content is 10 μg/g protein. More precisely, in a narrow range, the method isolates two fractions having 95.6% pure lactoferrin with cobalamin content of 9.13 ug/gm protein and 95.4% pure lactoferrin with much less amount of 1.85 μg/g protein (in PGPUB at least in example 3, Table 3, paragraphs [0077]-[0079]).
It is to be noted that applicant’s specification recites the phrase “allows the control of vitamin B12” (at least in PGPUB, paragraph [0002]). Therefore, this phrase is supported by the specification. However, still the phrase “controlled content of cobalamin” is confusing because, in specification, there is no explanation of this phrase with respect to the pattern of elution and amount of these two components present in respective fractions as stated and discussed above. Therefore, the phrase “controlled content of cobalamin” is confusing. This renders claim 1 indefinite.
Claim Rejections - 35 USC § 103
7. 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.
8. 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.
9. 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.
10. Claim(s) 1-2, 6 are rejected under 35 U.S.C. 103 as being unpatentable over Shigematsu et al. (EP 1466923 A1) in view of Knights et al. 2013/0011515 in view of Uchida et al. (EP 0556083 A1) and in view of Goldman et al. RU 2634859 C1 in view of Mozaffar et al. USPN 6096870 in view of Burling et al. USPN 5149647 in view of Rice USPN 5433847 A and further in view of Kawasaki et al. AU 3205993.
11. Regarding claims 1, 2, Shigematsu et al. discloses that a milk raw material is concentrated by membrane filtration and the resultant is brought into contact with a cation exchange resin (Abstract) to absorb lactoferrin.
Shigematsu et al. also discloses that the basic method for producing lactoferrin as proposed by the present invention consists of three steps: (1) concentrate a solution containing lactoferrin using a filter membrane with a pore size of 0.05 µM to 0.2 µM and thereby increase the lactoferrin content in the concentrate, (2) cause the concentrate to contact hydrophilic strong-acid cation-exchange resin to let the resin selectively adsorb lactoferrin, and (3) elute adsorbed lactoferrin from the aforementioned strong-acid cation-exchange resin into a saline solution of 1.0 M or above ([0010]).
Shigematsu et al. also discloses that the strongly acidic cation exchange resin which is Sulfopropyl -SP type (at least in [0018]).
Shigematsu et al. also discloses that the basic method proposed by the present invention as described above produces pure lactoferrin of 90 weight-percent or higher in recovered protein. By adjusting the feed volume through the strong-acid cation-exchange resin and also by adjusting the electrical conductivity of the feed to an appropriate level, high-purity lactoferrin of 98 weight-percent or above can be obtained in recovered protein only through normal saline elution ([0012]).
12. Regarding claim 1 step (a), Shigematsu et al. is silent about the claim limitation of “starting raw material previously concentrated by UF with a cutoff threshold of 10,000 kDa” as claimed in claim 1 (a).
Knights et al. discloses that when milk is ultrafiltered using a 10,000 MWCO membrane, all of the proteins and fat globules are retained, and the milk sugar, lactose, and the soluble minerals (sodium and potassium salts) pass through the membrane (at least in [0025]).
One of ordinary skill in the art before the effective filling date of the claimed invention would have been motivated to perform the UF filtration step using MWCO 10,000 kDa membrane in order to have the separation and removal of the milk sugar, lactose, and the soluble minerals (sodium and potassium salts) pass through the membrane ([0025]) to make retentate fraction rich in milk protein for further processing step.
Shigematsu et al. also discloses that in order to obtain high-purity lactoferrin in an efficient manner, one needs to determine the minimum resin-contact volume in accordance with a specific combination of milk material and strong-acid cation-exchange resin. Since this minimum contact volume is inversely proportional to the concentration ratio in the membrane filtration process, use of milk material in a concentrated form is more desirable in view of production efficiency ([0022]).
In addition, since a concentrated liquid obtained by concentrating milk raw materials with a membrane is used, the amount of raw material passed through the strongly acidic cation exchange resin may be smaller than in the conventional method, and the processing time of the strongly acidic cation exchange resin is reduced ([0013]).
Regarding the concentration of protein material (PM) between 40 and 72 g/L and when the starting raw material is whey, the concentration of protein material is between 20 and 100 gm/L , it is to be noted that it is within the skill of one of ordinary skill in the art to optimize the concentration in order to achieve the claimed range amount considering the known PM for skim milk is about 36g/L and whey (liquid whey from milk processing) is about 6-8.0 gm/L as evidenced by google search report.
Uchida et al. discloses that milk or whey protein including whey protein concentrate at concentrations of over 75% can be used in order to have lactoferrin in high yield (Under Detailed Description). Therefore, it meets the concentration range for claim 1 (a).
One of ordinary skill in the art before the effective filling date of the claimed invention would have been motivated to modify Shigematsu et al. with the teaching of Uchida et al. to make to make milk or whey protein concentrate having more protein material (PM) which meets claimed range value in order to have more lactoferrin load and therefore, lactoferrin in high yield (in Uchida, at least “Under Detailed Description”).
Absent showing of unexpected results, the specific amount of protein in the milk or whey concentrate is not considered to confer patentability to the claims. As the range amount of protein in the concentrate are variables that can be modified, among others, by adjusting the amount of volume of milk or whey to be reduced, the precise amount would have been considered a result effective variable by one having ordinary skill in the art at the time the invention was made. As such, without showing unexpected results, the claimed amount cannot be considered critical. Accordingly, one of ordinary skill in the art at the time the invention was made would have optimized, by routine experimentation, the amount of protein in milk or whey concentrate in Shigematsu et al., to amounts, including that presently claimed, in order to obtain the desired effect e.g. desired amount of protein in the concentrate (In re Boesch, 617 F.2d. 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. (In re Aller, 105 USPQ 223).
Regarding the pore size of the Sulfopropyl -SP type, Shigematsu et al. discloses Sulfopropyl -SP type cation exchange resin is used (at least in [0018]).
Shigematsu et al. does not specifically mention about (i) claimed diameter “greater than 100 microns” of the Sulfopropyl -SP type cation exchange resin and (ii) it is radial flow chromatography.
With respect to (i), it is to be noted that it is generally this value for such Sulfopropyl -SP type cation exchange resin in the instruction material of the company.
(Additionally), Goldman et al. also discloses that the method using sulfopropyl group containing cation exchanger polymer has particle size 160 micron which ensures its satisfactory performance with good sorption capacity, hydrodynamic property and can withstand pressure with good mechanical strength (page 4, paragraph 4 and paragraph 7 Starts with “Fig 2…” and page 5 under “d) “High sorption capacity”).
One of ordinary skill in the art before the effective filling date of the claimed invention would have been motivated to modify Shigematsu et al. to include the teaching of Goldman et al. to consider specified sulfopropyl group containing cation exchanger polymer has particle size 160 micron which ensures its satisfactory performance with good sorption capacity, hydrodynamic property and can withstand pressure with good mechanical strength (page 4, paragraph 4 and paragraph 7 Starts with “Fig 2…” and page 5 under “d) “High sorption capacity”).
With respect to (ii), Mozaffar et al. discloses that such chromatography separation can be performed using any type of chromatography column including radial flow chromatography column (col 17 lines 33-35, 45-47) in order to have many benefits including it has an advantage having at least much less pressure drop compared to axial flow packed tube etc. having uniform radial flow as disclosed by Rice et al. (col 1 lines 65-67, col 2 lines 1-5, claim 1 of Rice et al.). However, selection of radial flow chromatography column is also considered as the customer’s preferred design choice.
One of ordinary skill in the art before the effective filling date of the claimed invention would have been motivated to modify Shigematsu et al. to include the teaching of Mozaffar et al. who discloses that such chromatography separation can be performed using any type of chromatography column including radial flow chromatography column (col 17 lines 33-35, 45-47) and radial flow chromatography is preferred because it has unique superior properties including it has an advantage having at least much less pressure drop compared to axial flow packed tube etc. having uniform radical flow as disclosed by Rice et al. (col 1 lines 65-67, col 2 lines 1-5, claim 1 of Rice et al. ).
13. Regarding Claim 1 step (b) (i), Uchida et al. also discloses that One kg of a milk and related raw material and 0.2-100 g of a cation exchanger may generally be mixed (at least on page 4, paragraph four). Therefore, it meets the claim limitation of 40 and 500 times the volume of the resins BV as claimed in claim 1 (b) (i). This is also optimizable.
Absent showing of unexpected results, the specific amount of cation exchanger is not considered to confer patentability to the claims. As the lactoferrin load is variable which is based on the range amount of protein in the concentrate are variables therefore, the amount of resin with respect to the amount of milk or whey to be loaded that can be modified, among others, by adjusting the amount of volume of milk or whey with resin (cation exchanger) to be determined, the precise amount would have been considered a result effective variable by one having ordinary skill in the art at the time the invention was made. As such, without showing unexpected results, the claimed amount cannot be considered critical. Accordingly, one of ordinary skill in the art at the time the invention was made would have optimized, by routine experimentation, the volume of milk or whey concentrate with respect to volume of the resins BV in Shigematsu et al., to amounts, including that presently claimed, in order to obtain the desired effect e.g. desired amount of protein in the concentrate (In re Boesch, 617 F.2d. 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. (In re Aller, 105 USPQ 223).
Regarding the linear speed of the raw material passage between 1.0 and 4.0 m/h (i.e. contact time and flow rate), it is also in the instruction material from the company. Shigematsu et al. also discloses flow rate in terms of L/h ([0028]). However, this is within the skill of one of ordinary skill in the art to optimize the linear speed of the starting raw material passage which depends on the volume of starting material, its concentrated form having amount of protein material, volume of resin etc. in order to have optimum binding (saturation point) to have best quality with the best quantity lactoferrin in the final eluate.
As such, without showing unexpected results, the claimed amount cannot be considered critical. Accordingly, one of ordinary skill in the art at the time the invention was made would have optimized, by routine experimentation, the amount of protein in milk or whey concentrate in Shigematsu et al., to amounts, including that presently claimed, in order to obtain the desired effect e.g. desired amount of protein in the concentrate (In re Boesch, 617 F.2d. 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. (In re Aller, 105 USPQ 223).
Regarding claim 1 (b) (ii), “Rinsing with demineralized water”,
Shigematsu et al. also discloses that demineralized water was used for washing followed by that saline solution is used to elute ([0028]).
Regarding claim 1 step 1 (b) (iii), conductivity and elution step, Shigematsu et al. discloses that if the stock solution has electrical conductivity greater than 13 mS/cm provides better result with respect to more amount of lactoferrin compared to lactoperoxidase and more pure form of lactoferrin (at least in [0051], Table 2, above [0052]).
Shigematsu et al. also discloses that adjusting the electric conductivity to an appropriate value, high purity lactoferrin of 98% by weight or more in the recovered protein can be obtained only through normal saline elution (at least in [0012]).
Shigematsu et al. also discloses that the electrical conductivity of the milk raw material was 13 mS / cm or more. As described above, it has been found that the selectivity of lactoferrin for lactoperoxidase sharply increases.
Shigematsu et al. is silent about the “two step” and conductivity at step (iii) and (iv) to elute cation proteins as claimed in claim 1.
It is to be noted that Burling is used to combine the elution with two different concentrations of saline in combination with the electrical conductivity as taught by Shigematsu et al. in order to have an excellent purified lactoferrin free from lactoperoxidase.
Burling discloses a method to elute lactoperoxidase and lactoferrin using saline solution having a concentration of 0.1-0.4 M at about pH 6.5 for lactoperoxidase and at a pH of about 6.5 and the lactoferrin with a saline solution having a concentration of 0.5-2.0 M (at least in claim 1 of Burling).
One of ordinary skill in the art before the effective filling date of the claimed invention would have been motivated to modify Shigematsu et al. teaching of Burling to consider additionally, to elute lactoperoxidase and lactoferrin using saline solution having a concentration of 0.1-0.4 M at about pH 6.5 for lactoperoxidase and at a pH of about 6.5 and the lactoferrin with a saline solution having a concentration of 0.5-2.0 M (at least in claim 1 of Burling ) in order to make lactoperoxidase free from lactoferrin.
As described above, if we consider the combined teachings, it would have been
obvious that the two concentrations of saline for the elutions of two proteins lactoperoxidase followed by lactoferrin at different strengths of saline, would have obvious two different conductivity which would have been obvious greater than the initial electrical conductivity of the milk raw material was 13 mS / cm or more as disclosed by Shigematsu et al. (at least in Table 2 and claim 5 of Shigematsu et al.
Also, it is within the skill of one of ordinary skill in the art to optimize the highest elution from within the range value of saline strength and also the conductivity for the best elution peak. Therefore, electrical conductivity at the elution step is optimizable.
As such, without showing unexpected results, the claimed amount cannot be considered critical. Accordingly, one of ordinary skill in the art at the time the invention was made would have optimized, by routine experimentation, the electrical conductivity at the two steps of elution in Shigematsu et al., to amounts, including that presently claimed, in order to obtain the desired effect e.g. desired best sharp peak of elution (i.e. best amount and purity) of the respective proteins separately, one of them is lactoferrin (In re Boesch, 617 F.2d. 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. (In re Aller, 105 USPQ 223).
Regarding volume of the saline solution to be used for elution, the combinations of prior arts do not specifically teach the claimed volume of saline solution is between 2/3-6 BV, however, this is also optimizable. It is within the skill of one of ordinary skill in the art to optimize the volume of the saline solution (BV) in order to have the best elution with sharp peak.
As such, without showing unexpected results, the claimed amount cannot be considered critical. Accordingly, one of ordinary skill in the art at the time the invention was made would have optimized, by routine experimentation, the electrical conductivity at the two steps of elution in Shigematsu et al., to amounts, including that presently claimed, in order to obtain the desired effect e.g. desired best sharp peak of elution (i.e. best amount and purity) of the respective proteins separately, one of them is lactoferrin (In re Boesch, 617 F.2d. 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. (In re Aller, 105 USPQ 223).
14. Regarding claim 1 steps (c), (d), (e), (f), Burling et al. discloses that the saline solution with lactoferrin is concentrated, desalted and freeze dried (claim 5 of Burling et al.). Step (f) is optional. However, drying is disclosed. Mozaffar et al. discloses that such a product can be dried after UF and diafiltration step using spray drying method (at least in col 41 lines 50-52).
However, Burling et al. is silent about cut-off threshold value of 10-20 kDa.
Kawasaki et al. has disclosed that the eluted lactoferrin solutions were concentrated and desalted with an ultrafiltration membrane having molecular weight cut-off of 10,000. respectively, and lyophilized to give final purified product (page 8, paragraph 1; e.g. para starts with “The eluted lactoperoxidase……and lactoferrin…. cut-off 10,000.”).
One of ordinary skill in the art before the effective filling date of the claimed invention would have been motivated to modify Shigematsu et al. in view of Burling et al. to use the teaching of Kawasaki et al. to further purify the eluted lactoferrin solutions to concentrate and desalt with an ultrafiltration membrane having molecular weight cut-off of 10,000 respectively, and lyophilized to give final purified product (page 8, paragraph 1).
Mozaffar et al. discloses that the lactoferrin fraction can further be diafiltered (col 5 lines 22-23). It is to be noted that diafiltration after UF provides further removal of residual small molecule contaminants e.g. sodium chloride etc. using demineralized water to be removed.
One of ordinary skill in the art before the effective filling date of the claimed invention would have been motivated to modify Shigematsu et al. in view of Burling et al. and Kawasaki et al. to use the teaching of Mozaffar et al. that the lactoferrin fraction can further be diafiltered (col 5 lines 22-23) after UF provides further removal of residual small molecule contaminants e.g. sodium chloride etc. using demineralized water to be removed.
15. Regarding claim 6, Shigematsu et al. discloses that the lactoferrin isolated and purified by this method can be used in food materials including human and animal food ([0066]).
16. Claims 3, 4 and 5 are rejected under 35 U.S.C. 103 as being unpatentable over Shigematsu et al. (EP 1466923 A1) in view of Knights et al. 2013/0011515 in view of Uchida et al. (EP 0556083 A1) and in view of Goldman et al. RU 2634859 C1 in view of Mozaffar et al. USPN 6096870 in view of Burling et al. USPN 5149647 in view of Rice USPN 5433847 A as applied to claim 1 and further in view of Roy et al. USPN 3035983 A.
17. Regarding claims 3,4, it is to be noted that if we consider the cobalamin is 5 micrograms, then claim 3, 4 are identical and one of ordinary skill in the art can confirm which fraction has 5 micrograms contain lactoferrin by using conventional spectrometric analysis.
18. Shigematsu et al. are silent about the specific lactoferrin with cobalamin less than or equal to 5 microgram/gm cobalamin as claimed in claim 3 and lactoferrin with cobalamin more than or equal to 5 microgram/gm cobalamin as claimed in claim 4.
Roy et al. discloses that cobalamin and peptide complex can be measured using spectroscopic measurement (optical density) [col 2 lines 32-36).
Burling et al. discloses that lactoferrin is eluted with a saline solution 0.5-2.0 M (claim 1 of Burling) and peak can be 0.9 M solution (Fig 2) (col 4 lines 60-62). Therefore, it would have been obvious and it is known to one of ordinary skill in this art to collect eluates from after 0.5 -2M, few aliquotes to determine the fraction having how much cobalamin is attached with lactoferrin because, the eluates will vary with different amounts of cobalamin.
Therefore, one of ordinary skill in the art before the effective filling date of the claimed invention would have been motivated to modify Shigematsu et al. to include the teaching of Burling et al. discloses that lactoferrin is eluted with a saline solution 0.5-2.0 M (claim 1 of Burling) and peak can be 0.9 M solution (Fig 2) (col 4 lines 60-62). Therefore, it would have been obvious and it is known to one of ordinary skill in this art to collect eluates from after 0.5 -2M, few aliquots (claim 1 of Burling) and to determine the cobalamin and peptide complex by using spectroscopic measurement (optical density) [col 2 lines 32-36) in order to determine which fraction has the desired amount of cobalamin including less than or equal to 5.0 microgram/g or equal to or more than 5 µg/g.
19. Regarding claim 5, it is to be noted that the disclosed cationic whey protein is identical to the claimed cationic whey protein and therefore, it will have the identical property of its use “in the prevention and/or the treatment of a vitamin B12 deficient absorption in patients who have undergone gastrectomy or chronically treated with proton pump inhibitors PPI”.
20. Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Shigematsu et al. (EP 1466923 A1) in view of Knights et al. 2013/0011515 in view of Uchida et al. (EP 0556083 A1) and in view of Goldman et al. RU 2634859 C1 in view of Mozaffar et al. USPN 6096870 in view of Burling et al. USPN 5149647 in view of Rice USPN 5433847 A and further in view of AU 3205993 as applied to claim 2 and further in view of Schmitt et al. EP 1844758 A1.
21. Regarding claim 7, Shigematsu et al. is silent about the use of lactoferrin in non-food product.
Schmitt et al. discloses that lactoferrin can be used in cosmetic composition as an active ingredient with whey protein micelle (at least in page 11, fifth paragraph e.g. para starts “Also, in their …. lactoferrin (4th line) ……etc.”. ).
One of ordinary skill in the art before the effective filling date of the claimed invention would have been motivated to modify Shigematsu et al. with the teaching of Schmitt et al. to use lactoferrin in cosmetic composition as an active ingredient with whey protein micelle (at least in page 11, fifth paragraph e.g. para starts “Also, in their …. lactoferrin (4th line)……etc.”. ).
Response to arguments
22. Applicants’ arguments and amendments have been considered. Applicants’ arguments and amendments of independent claim 1 overcome the rejections of record. Therefore, a new secondary prior art by Knights et al. (US 2013/0011515) has [0025] 10 kDa has been considered in order to perform a is used to teach the previously concentrated step to concentrate raw material skim milk using 10 kDa MWCO UF membrane which eliminates most of the small molecules e.g. lactose from the raw material to make relatively lactose free concentrated raw skim milk for further treatment.
However, the phrase “controlled content of cobalamin” has 112 second paragraph issues and did 112 rejections as discussed above.
23. Applicants argued that “The cited references should at least now fail to provide the above recited features in combination with other features recited in amended claim 1.
(a) First, Rice, Schmitt, and Roy do not describe a process for purifying lactoferrin. A person skilled in the art would not have found any apparent reason and would not have been encouraged to consult them and therefore would not have taken their teaching into account. The technical fields of these three documents and the present invention are different.
In response to (a), Rice, Schmitt, and Roy are used as secondary prior art. Rice discloses the advantage of using Radial flow chromatography. Therefore, it can be considered to modify chromatographic separation with proper teaching suggestive motivation (TSM) to separate at the step of claim 1(b) (i).
According to MPEP 2143.01, “Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis)”.
However, note that while Rice et al. does not disclose all the features of the present claimed invention, Rice et al. is used as teaching reference, and therefore, it is not necessary for this secondary reference to contain all the features of the presently claimed invention, In re Nievelt, 482 F.2d 965, 179 USPQ 224, 226 (CCPA 1973), In re Keller 624 F.2d 413, 208 USPQ 871, 881 (CCPA 1981). Rather this reference teaches a certain concept, namely the advantage of using radial flow chromatography because it has unique superior properties including it has an advantage having at least much less pressure drop compared to axial flow packed tube etc. having uniform radical flow as disclosed by Rice et al. (col 1 lines 65-67, col 2 lines 1-5, claim 1 of Rice et al. ), and in combination with the primary reference, discloses the presently claimed invention.
Regarding Schmitt et al., Schmitt et al. is used as secondary prior art to address the use of lactoferrin in cosmetic composition. Therefore, the argument made for Schmitt et al. that “the technical fields of Schmitt et al. for the present invention are different” is not relevant.
However, note that while Schmitt et al. does not disclose all the features of the present claimed invention, Schmitt et al. is used as teaching reference, and therefore, it is not necessary for this secondary reference to contain all the features of the presently claimed invention, In re Nievelt, 482 F.2d 965, 179 USPQ 224, 226 (CCPA 1973), In re Keller 624 F.2d 413, 208 USPQ 871, 881 (CCPA 1981). Rather this reference teaches a certain concept, namely the use of lactoferrin in cosmetic composition as an active ingredient with whey protein micelle (at least in page 11, fifth paragraph e.g. para starts “Also, in their …. lactoferrin (4th line) ……etc.”. ).
Regarding Roy et al., Roy et al. is used as secondary prior art to teach the method of measuring cobalamin and peptide complex using spectroscopic measurement (optical density) [col 2 lines 32-36) in order to determine their amounts in the collected fractions as collected after chromatographic separation followed by elution step. The method of Roy et al. is applicable to determine their amounts in any related product including food composition having these components in the composition.
According to MPEP 2143.01, “Obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis)”.
However, note that while Roy et al. does not disclose all the features of the present claimed invention, Roy et al. is used as teaching reference, and therefore, it is not necessary for this secondary reference to contain all the features of the presently claimed invention, In re Nievelt, 482 F.2d 965, 179 USPQ 224, 226 (CCPA 1973), In re Keller 624 F.2d 413, 208 USPQ 871, 881 (CCPA 1981). Rather this reference teaches a certain concept, namely the method of measuring cobalamin and peptide complex can be measured using spectroscopic measurement (optical density) [col 2 lines 32-36) and in combination with the primary reference, discloses the presently claimed invention.
(b) Second, applicant argued on third page, mid-section, in remarks that “the applicant considers Shigematsu to be the closest prior art in that it relates to a process for producing lactoferrin, using a strong acid hydrophilic cation exchange resin. The technical effect of the present application is the production of isolate of cationic whey proteins of high purity of lactoferrin having a controlled content of cobalamin, as demonstrated in the experimental section of the present Application (in specification, Example 3). Shigematsu does not describe that the lactoferrin produced with its process has a controlled content of cobalamin. No cited prior art mentions that the lactoferrin having a controlled content of cobalamin. Then, the person skilled in the art is not encouraged to modify Shigematsu in view of Uchida, Goldman, Mozaffar, Burling, Rice, Kawasaki and/or Roy.
In response to (b), as mentioned above, the phrase “controlled content of cobalamin” has 112 first and second paragraph rejection and it is not clear to one of ordinary skill in the art what is meant by this limitation. However, examiner used a new secondary prior art by US 2013/0011515 ([0025]) who discloses that raw material skim milk can be previously concentrated using 10 kDa MWCO UF membrane which eliminates most of the small molecules e.g. lactose from the raw material to make relatively lactose free concentrated raw skim milk for further treatment.
(c ) Third, applicants argued on fourth page, and first paragraph of fifth page, in remarks that “Moreover, the starting raw material in the present application is concentrated by reverse osmosis (RO), nanofiltration (NF) or ultrafiltration (UF). For UF, the membrane has a cutoff threshold not more than 10kDa”. Applicants also presented on fourth page, a figure from one reference and argued that the person skilled in the art understands that the membranes used in the present Application to concentrate the raw material have a pore size from 0.1 nm to 5 nm (considering the cutoff of 10kDa). Therefore, accordingly, applicant’s position is, “In Shigematsu [0010], the solution containing lactoferrin is concentrated using a filter membrane with a pore size of 0.05µm to 0.2µm . From the table 1, the person skilled in the art understand that the use of a pore size of filter less than 0.05µm is not recommended/desirable to obtain lactoferrin with high purity. The person skilled in the art would then be deterred/discouraged from using membrane with a pore size from 0.1 nm to 5 nm (0.0001 µm to 0.005 µm)”.
In response to (c ), , it is to be noted that firstly, claim 1 claims UF membrane filtration using MWCO 10 kDa. However, claim 1 does not claim the pore size as alleged by the applicants and therefore, there is no issue to one person skilled in the art to be deterred/discouraged from using membrane with a pore size from 0.1 nm to 5 nm (0.0001 µm to 0.005 µm)”. In addition, if we consider applicants presented Fig on page 4, in remarks, MWCO 10,000 kDa may have pore diameter range which covers broad range of from about 1nm-above about 200 nm.
(d) Fourth , applicants also argued on fifth page second paragraph that “at last, the cobalamin is complex with a cationic protein with a molecular weight of 43 kDa [0046, present Application], while lactoferrin has a molecular weight of 80kDa. The paragraph [0047] describes that "the behavior of this complex during the treatment by cation exchange chromatography is close to that of lactoferrin". In other words, the separation of the cobalamin-transcobalamin complex from lactoferrin is more difficult than the separation of lactoperoxidase (Shigematsu) from lactoferrin. The Inventors have gained the insight and thus determined the optimum conditions to obtain high purity of lactoferrin having a controlled content of cobalamin. Nothing in the prior art cited highlights this technical difficulty and no proposals to resolve it are described”.
In response to (d), applicants’ argument is primarily that the separation of the cobalamin-transcobalamin complex from lactoferrin is more difficult than the separation of lactoperoxidase (Shigematsu) from lactoferrin
As discussed above, Shigematsu et al. is modified with the teaching of Burling (at least in claim 1 of Berlin et al.) to make lactoperoxidase free from lactoferrin which meets claim 1 (iii) and (iv). Burling discloses a method to elute lactoperoxidase and lactoferrin using saline solution having a concentration of 0.1-0.4 M at about pH 6.5 for lactoperoxidase and at a pH of about 6.5 and the lactoferrin with a saline solution having a concentration of 0.5-2.0 M (at least in claim 1 of Burling).
As discussed above, Roy et al. teaches the method of measuring cobalamin and peptide complex can be measured using spectroscopic measurement (optical density) [col 2 lines 32-36) and in combination with the primary reference, discloses the presently claimed invention as claimed in claims 3,4.
Therefore, it is within the skill of one of ordinary skill in the art to collect fractions during elution of lactoferrin with time intervals, from the teaching of Berlin et al. and to measure the contents of cobalamin and lactoferrin peptide complex fractions from the teachings of Roy et al.(col 2 lines 32-36) in order to have desired fractions having desired amounts of these two components of choice.
Therefore, it is free from lactoperoxidase. Applicants argument is lactoperoxidase separation is easy than
It is also to be noted that the combined teaching meets the identical methods with identical cation exchange resins (Sulphopropyl SP type) to make pure lactoferrin. Therefore, as the disclosed membranes used for UF followed by radial flow chromatography with resin, which is identical to claimed membranes used for UF followed by radial flow chromatography and claimed cation exchange resins (Sulphopropyl SP type) resin, then the eluate will have identical pure lactoferrin and the purity with the presence of cobalamin will remain same trend e.g. with more purity from and above 90% pure lactoferrin, the cobalamin will be gradually less (reverse) and it can be determined by and it is within the skill of one of ordinary skill in the art to determine their level at the beyond 90% purity fraction of lactoferrin. This is not an unexpected result.
As there are no further arguments the rejection is made as final.
Conclusion
24. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning the communication or earlier communications from the examiner should be directed to Bhaskar Mukhopadhyay whose telephone number is (571)-270-1139.
If attempts to reach the examiner by telephone are unsuccessful, examiner’s supervisor Erik Kashnikow, can be reached on 571-270-3475. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BHASKAR MUKHOPADHYAY/
Examiner, Art Unit 1792
/ERIK KASHNIKOW/Supervisory Patent Examiner, Art Unit 1792