DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The status of the claims stands as follows:
Pending claims: 1-5, 21-35
Withdrawn claims: 1-3, 34-35
Cancelled claims: 6-20
Claims currently under consideration: 4-5, 21-33
Currently rejected claims: 4-5, 21-33
Allowed claims: None
Election/Restrictions
Applicant's election with traverse of Group II (claims 4-5, 21-33) in the reply filed on 06/10/2026 is acknowledged. The traversal is on the ground(s) that Groups I-IV are so related such that the search and examination of Groups I-IV will not result in a serious search burden for the examiner (Applicant’s Remarks, page 3, 2nd paragraph).
This is not found persuasive because the restriction was made on the basis of Groups I-IV lacking unity of invention due to the technical feature shared between the groups (i.e., yeast cell wall having the features recited in claim 1) not being a special technical feature over prior art references Calabotta and Khan. The restriction was not made on the basis of there being a search burden on the Examiner. Therefore, Applicant’s argument regarding there being no burden in the search and examination of Groups I-IV is unpersuasive.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-3 and 34-35 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Groups I and III-IV, there being no allowable generic or linking claim.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Interpretation
The amounts of “1-10 0/00” will be interpreted as meaning 1-10 parts per thousand.
Claim Objections
Claims 21-25, 29, and 31 are objected to because of the following informalities:
In claim 21, “characterized in that the protease in step (2)” should be read as “characterized in that the protease in the protease enzymolysis in step (2)”.
In claim 22, “that the protease is one or a combination” should be read as “that the protease in the protease enzymolysis of step (2) is one or a combination”.
In claim 23, “that the protease comprises” should be read as “that the protease in the protease enzymolysis comprises”.
In claim 24, “characterized in that the proteases are neutral protease and bromelain, or neutral protease, bromelain and papain, or papain, neutral protease, alkaline protease, and bromelain” should be read as “characterized in that the protease in the protease enzymolysis comprises a combination of neutral protease and bromelain; a combination of neutral protease, bromelain and papain; or a combination of papain, neutral protease, alkaline protease, and bromelain”.
In claim 25, “enzymolysis temperature of the protease is 30-60°C, the enzymolysis pH of the protease is 4.5-7.0 and the enzymolysis time of the protease is 6-10 h” should be read as “temperature of the protease enzymolysis is 30-60°C, the pH of the protease enzymolysis is 4.5-7.0 and the time of the protease enzymolysis is 6-10 h”.
In claim 29, “that the enzyme used in the secondary enzymolysis is glucanase and cellulase, or glucanase, mannanase and cellulase, or glucanase, mannanase, cellulase, and amylase” should be read as “that the enzyme used in the secondary enzymolysis is a combination comprising glucanase and cellulase; a combination comprising glucanase mannanase and cellulase; or a combination comprising glucanase, mannanase, cellulase, and amylase”.
In claim 31, “Saccharomyces cerevisiae” should be read as “Saccharomyces cerevisiae”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 5 and 33 are 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 (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 5 recites a salt concentration of 2-5.5%. However, there is no unit of measurement associated with this percentage (e.g., wt.%; vol.%). Therefore, the claim is indefinite.
For the purpose of this examination, the percentage will be interpreted as being a weight percentage.
Claim 33 recites that “the carbon source is 6,000-8,00 parts, the nitrogen source is 400-700 parts, and the phosphorus source is 300-600 parts”. However, it is not clear as to what these components are a part of (e.g., an extrinsic feed source composition comprising a carbon source, nitrogen source, and phosphorus source; a fermentation medium for the yeast); therefore, it is not clear as to what serves as the basis from which to determine whether the carbon, nitrogen, and phosphorus sources are present in the claimed amounts. It is also not clear as to what units are associated with the “parts” (e.g., parts based on weight; parts based on volume); or how many parts total are present (e.g., parts per million based on the total weight of a composition comprising the carbon, nitrogen, and phosphorus sources; parts per million based on the total weight of only the carbon, nitrogen, and phosphorus sources). For these reasons, it is unclear as to what amounts are required by claim 33.
For the purpose of this examination, claim 33 will be interpreted as requiring a carbon source, a nitrogen source, and a phosphorus source be present in the fermentation medium in any weight percentages thereof.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 4/1, 5, 21-22, and 25-33 are rejected under 35 U.S.C. 103 as being unpatentable over Kaur (Kaur et al., “Structural Features, Modification, and Functionalities of Beta-Glucan”, 2020, Fibers, 8, 1, doi:10.3390/fib8010001) in view of Hu (CN109207384A; English translation relied on for citations) and Saarinen (US 2011/0250235).
Regarding claim 4/1, Kaur teaches that the functional properties of β-glucan are linked to the source, the molecular weight, and the structure of the β-glucan (abstract). Kaur teaches that β-glucan may be modified by enzyme hydrolysis and chemical processes, which are well-known methods of modification, in order to obtain the desired molecular weight and structural features of β-glucan (abstract; page 2, 1st paragraph). Kaur teaches that yeast cell walls have become a source of β-glucan due to the advancement in research (page 2, paragraph under section 2). Kaur discloses that enzymatic hydrolysis has been performed using glucanase and cellulase (page 16, paragraph under section 3.3; page 18, 1st paragraph). Kaur also discloses that chemical modification has been performed using acid treatment (page 6, Fig. 6). Kaur teaches that these modification methods may be combined such as chemo-enzymatic processes to potentially produce significant changes in the bio-functional characteristics of β-glucan (page 24, paragraph under section 5). Kaur also teaches that the high molecular weight of native β-glucan makes it difficult for β-glucan to act as an immune stimulator (page 6, paragraph), thereby at least suggesting that the disclosed modification methods decrease the molecular weight of the β-glucan to provide immune stimulation effects.
As described above, Kaur suggests a method of obtaining modified β-glucan from yeast through combining enzymatic and chemical processes, wherein enzymatic processes may include glucanase and/or cellulase which are enzymes recited in the secondary enzymolysis of step (2) of the presently claimed method. Kaur does not teach that the method comprises all the features of the steps recited in present claim 4. Kaur also does not teach that the method produces a composition comprising a yeast cell wall characterized in that glucan with a relative molecular weight of 80-200 kDa accounts for more than 99% of total glucan mass in the yeast cell wall and the glucan content is 20-40% by weight of the yeast cell wall as recited in present claim 1.
However, Hu teaches a method of modifying β-glucan in a yeast cell wall in order to improve the immunity stimulation ability of β-glucan, wherein the method comprises (1) subjecting a raw material containing yeast to autolysis to break the yeast cell wall to obtain cell wall milk; (2) subjecting the yeast cell wall milk obtained in step (1) to protease enzymolysis (corresponding to hydrolysis with alkaline protease and papain) and secondary enzymolysis successively to obtain an enzymatic hydrolysate (page 2, lines 3-7; page 5, line 43- page 6, line 8). Hu teaches that the enzyme used in the secondary enzymolysis may be cellulase and glucanase (page 6, lines 1-8). Hu teaches that these steps produce a composition comprising a modified yeast cell wall containing β-glucan in an amount of 25-50% β-glucan (page 5, lines 8-11), which is considered to encompass the claimed β-glucan content recited in present claim 1. The selection of a value within the encompassing range renders the claimed content obvious. MPEP §2144.05.I. Hu also teaches that these steps modify the molecular weight of a yeast cell wall so that more than 99% of the total glucan mass has a relative molecular weight of 3.0x105-1.0x106 (page 5, lines 12-13). This value is considered to equate to 300-1,000 kDa, which is greater than the claimed relative molecular weight of 80-200 kDa.
It would have been obvious for a person of ordinary skill in the art prior to the effective filing date of the present invention to have modified the method of Kaur to comprise (1) subjecting a raw material containing yeast to autolysis to break the yeast cell wall to obtain cell wall milk; and (2) subjecting the yeast cell wall milk obtained in step (1) to protease enzymolysis and secondary enzymolysis successively to obtain an enzymatic hydrolysate (page 5, line 43- page 6, line 8) as taught by Hu. Since Kaur suggests a method of obtaining modified β-glucan from yeast cell wall through combining enzymatic and chemical processes, wherein the enzymatic processes may include glucanase and/or cellulase and wherein these modification methods decrease the molecular weight of the β-glucan to provide immune stimulation effects, but Kaur does not specifically disclose method steps for enzymatic hydrolysis of β-glucan from yeast cell wall, a skilled practitioner would have been motivated to consult an additional reference such as Hu in order to determine suitable method steps for enzymatic hydrolysis of β-glucan from yeast cell wall using the enzymes glucanase and/or cellulase in order to reduce molecular weight and improve immune stimulation ability of the β-glucan, thereby rendering the steps (1) and (2) of present claim 4 obvious.
The combination of Kaur and Hu does not teach that the method comprises step (3) as recited in present claim 4. The combination of Kaur and Hu also does not teach that the method produces a composition comprising a yeast cell wall characterized in that glucan with a relative molecular weight of 80-200 kDa accounts for more than 99% of total glucan mass in the yeast cell wall as recited in present claim 1.
However, Saarinen teaches an immunostimulatory composition produced from yeast cell wall, wherein the composition comprises β-glucan [0021]-[0026]. Saarinen teaches that the β-glucan in the composition may be modified by a method comprising enzymatic hydrolysis followed by acidolysis (corresponding to acid hydrolysis) (Fig. 1; [0016]). Therefore, Saarinen discloses a step (3) of subjecting an enzymatic hydrolysate to acidolysis as recited in present claim 4.
It would have been obvious for a person of ordinary skill in the art to have modified the method of modified Kaur to comprise (3) subjecting an enzymatic hydrolysate to acidolysis as taught by Saarinen. Since Kaur suggests a method of obtaining modified β-glucan from yeast cell wall through combining enzymatic and chemical processes, wherein the chemical process may comprise acid treatment and wherein these modification methods decrease the molecular weight of the β-glucan to provide immune stimulation effects; and since Hu teaches enzymatic processes to modify the molecular weight of the β-glucan to provide immune stimulation effects, but neither Kaur nor Hu disclose specific steps of chemical processing using acid to modify molecular weight of β-glucan to provide immune stimulation effects, a skilled practitioner would have been motivated to consult an additional reference such as Saarinen in order to determine a suitable method of acidolysis, thereby rendering step (3) of present claim 4 obvious.
The combination of Saur, Hu, and Saarinen do not specifically disclose that the method produces a composition comprising a yeast cell wall characterized in that glucan with a relative molecular weight of 80-200 kDa accounts for more than 99% of total glucan mass in the yeast cell wall as recited in present claim 1. However, Hu teaches that after steps (1) and (2) are performed, more than 99% of the total glucan mass in the yeast cell wall has a relative molecular weight of 300-1,000 kDa (page 5, lines 12-13), which is larger than the claimed relative molecular weight. However, after performing the acidolysis of step (3) on the yeast cell wall of step (2), the molecular weight of the glucan would decrease from 300-1,000 kDa. Therefore, it is presumable that after performing step (3), more than 99% of the total glucan mass in the yeast cell wall would have a maximum relative molecular weight of less than 1,000 kDa and a minimum relative molecular weight of greater than 0 kDa, thereby providing a range which encompasses the range recited in present claim 1. The selection of a value within the encompassing range renders the claimed content obvious. MPEP §2144.05.I.
Further, the Office does not have laboratory facilities to test claim limitations drawn toward results of practicing the method as claimed. Accordingly, such features of the yeast cell wall recited in present claim 1 do not serve to distinguish the product as claimed from the prior art and are thus considered obvious to one having ordinary skill in the art.
Regarding claim 5, modified Kaur teaches the invention as described above in claim 4/1, including the autolysis in step (1) is carried out at a salt concentration of 3-5%; a pH of 5.5-6.5; and a temperature of 55-75°C (Hu, page 2, lines 58-60). These values are considered to fall within the claimed ranges.
Regarding claim 21, modified Kaur teaches the invention as described above in claim 4/1, including that the protease used in the protease enzymolysis in step (2) may be alkaline protease added in an amount of 3-50/00 based on the dry matter mass of the yeast cell wall milk (Hu, page 3, lines 1-3), which falls within the claimed range.
Regarding claim 22, modified Kaur teaches the invention as described above in claim 4/1, including that the protease used in the protease enzymolysis in step (2) may be papain, alkaline protease (Hu, page 3, lines 1-3), or bromelain (Saarinen [0158]).
Regarding claim 25, modified Kaur teaches the invention as described above in claim 4/1, including the protease enzymolysis temperature may be 40-52°C, the protease enzymolysis pH may be 4.0-6.0, and the protease enzymolysis time may be 7-10 hours (Hu, page 3, lines 15 and 26). The disclosed temperature and time falls within the claimed ranges. The disclosed pH overlaps the claimed pH range. The selection of a value within the overlapping range renders the claimed content obvious. MPEP §2144.05.I.
Regarding claim 26, modified Kaur teaches the invention as described above in claim 4/1, including the amount of enzyme used in the secondary enzymolysis is 0.2-10/00 based on the dry matter mass of the yeast cell wall milk (page 3, lines 1-3), which overlaps the claimed concentration. The selection of a value within the overlapping range renders the claimed content obvious. MPEP §2144.05.I.
Regarding claim 27, modified Kaur teaches the invention as described above in claim 4/1, including the secondary enzymolysis temperature may be 40-67°C, the secondary enzymolysis pH may be 4.5-6.5, and the secondary enzymolysis time may be 6-12 hours (Hu, page 3, lines 21 and 32). The disclosed pH and time falls within the claimed ranges. The disclosed temperature encompasses the claimed pH range. The selection of a value within the encompassing range renders the claimed range obvious. MPEP §2144.05.I.
Regarding claims 28 and 29, modified Kaur teaches the invention as described above in claim 4/1, including the enzyme used in the secondary enzymolysis may be glucanase and cellulase (Hu, page 3, lines 1-3).
Regarding claim 30, modified Kaur teaches the invention as described above in claim 4/1, including the acidolysis pH may be about 2-3, the acidolysis temperature may be about 30-90°C, and the acidolysis time may be about 2-48 hours (Saarinen [0104]). The disclosed pH falls within the claimed range. The disclosed time and temperature overlap the claimed ranges. The selection of a value within the overlapping range renders the claimed ranges obvious. MPEP §2144.05.I.
Regarding claims 31, 32, and 33, modified Kaur teaches the invention as described above in claim 4/1, including that the yeast-containing raw material of step (1) may be obtained by fermentation of a Saccharomyces cerevisiae strain at a fermentation pH of 4.0-6.0, a fermentation temperature of 28-30°C, and a fermentation time of 16-24 hours (Hu, page 3 line 52; page 6, lines 15-18). The disclosed pH, temperature, and time fall within the claimed ranges. Hu also teaches that the fermentation medium comprises a carbon source, a nitrogen source, and a phosphorus source (corresponding to NH4H2PO4) (page 6, lines 15-18; page 7, lines 5-7).
Claims 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over Kaur (Kaur et al., “Structural Features, Modification, and Functionalities of Beta-Glucan”, 2020, Fibers, 8, 1, doi:10.3390/fib8010001) in view of Hu (CN109207384A; English translation relied on for citations) and Saarinen (US 2011/0250235) as applied to claim 4/1 above, and further in view of Pharmacy (“Ficin”, 2020, Pharmacy 180, https://www.pharmacy180.com/article/ficin-341/).
Regarding claims 23 and 24, modified Kaur teaches the invention as described above in claim 4/1, including the protease in the protease enzymolysis may comprise papain, bromelain, an alkaline protease, and an enzyme from Ficus glabrata wherein the enzyme may have an optimum proteolytic activity at about pH 7 (Hu, page 3, lines 1-3; Saarinen, [0158]).
Modified Kaur does not teach that the protease in the protease enzymolysis further comprises a neutral protease as recited in present claims 23 and 24.
However, Pharmacy teaches that a protease enzyme from Ficus glabrata is ficin (1st-2nd paragraphs under “Biological Source”). Pharmacy teaches that ficin generally has an optimum pH of 5-8 (paragraph under “Characteristics”). Since the optimum range of the enzyme spans the neutral pH range, ficin is considered to qualify as a neutral protease.
It would have been obvious for a person of ordinary skill in the art to have modified the enzyme from Ficus glabrata of modified Kaur to be ficin as taught by Pharmacy. Since Saarinen discloses that the protease may be from Ficus glabrata, wherein the enzyme has an optimum pH at above pH 7, but does not disclose such a protease, a skilled practitioner would have been motivated to consult an additional reference such as Pharmacy in order to determine a suitable protease, thereby rendering a protease combination comprising neutral protease obvious. As such, the combination of prior art teaches that the protease may be a combination comprising neutral protease, bromelain, papain, and alkaline protease as recited in present claims 23 and 24.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kelly Kershaw whose telephone number is (571)272-2847. The examiner can normally be reached Monday - Thursday 9:00 am - 4:00 pm.
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/KELLY P KERSHAW/Examiner, Art Unit 1791
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