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 .
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 1-12 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 regards as the invention.
In claim 1, the term “high-concentration silk fibroin solution” is a vague, relative term, there being no clear standard for identifying an encompassed range of values of the parameter;
“to membrane clarification process” and “perform desalination process” are each of confusing syntax; and
the absence of the term “and” between “S3” and “S4” makes the claim ambiguous as to whether or not step “S4” is the last in the series of steps of “the following steps”.
In claim 2, the terms “high-concentration”, “high flow rate”, “high flux” and “low adsorption” are each vague, relative terms, there being no clear standards for identifying encompassed ranges of “high”, vs. “medium” or “low” values of the respective parameters; and,
the terminology “such as”, “preferably” and “most preferably”, in each instance, makes the claim ambiguous as to whether the clauses which immediately follow are positively recited and required claim limitations, and the scope of terms which qualify as “such as” is unclear.
In claim 3, the presence of two comma’s following “step S3” is grammatically confusing;
the terminology “such as”, “preferably” and “more preferably”, in each instance, makes the claim ambiguous as to whether the clauses which immediately follow are positively recited and required claim limitations, and the scope, or metes and bounds of terms which are encompassed by “such as” concerning volume of the purified water being added is unclear.
In claim 4, the terminology “preferably” makes the claim ambiguous as to whether the clause which immediately follows is a positively recited and required claim limitation.
In claim 5, the terminology “preferably”, “more preferably”, “even more preferably” and “most preferably”, in each instance, makes the claim ambiguous as to whether the clauses which immediately follow are positively recited and required claim limitations.
In claim 6, the scope , or metes and bounds of terms which are encompassed by “inorganic salt is selected…etc” is unclear.
In claim 7, the absence of the term “and” between “S11” and “S12” makes the claim ambiguous as to whether or not step “S4” is the last in the series of steps of “the following steps”.
In claim 8, the terminology “such as” and “preferably”, in each instance, makes the claim ambiguous as to whether the clauses which immediately follow are positively recited and required claim limitations, and “is most preferable also makes the claim unclear as to whether “material…a multilayer glass fiber” is a positively recited and required claim limitation; and
the terms “strong clarification capacity”, “high dirt-holding capacity”, “high total flux”, “broad chemical compatibility” and “low non-specific adsorption” are each vague, relative terms, there being no clear standards for identifying encompassed ranges of values of the respective parameters which are “strong”, “high”, “broad” and “low”, respectively.
In claim 9, the terminology “preferably”, “more preferably” and “even more preferably” in each instance, makes the claim ambiguous as to whether the clauses which immediately follow are positively recited and required claim limitations;
the term “high-concentration silk fibroin solution” is a vague, relative term, there being no clear standard for identifying an encompassed range of values of the parameter; with
“the process conditions” lacking antecedent basis and unclear as to the scope of what is encompassed by “process conditions” (does this refer to variables such as times, flow rates, and pressures at which steps S1, S2, S3 and S4 are performed?).
In claim 10, the terminology “preferably” makes the claim ambiguous as to whether the clause which immediately follows is a positively recited and required claim limitation.
In claim 12, the terminology “preferably”, “more preferably” and “even more preferably” in each instance, makes the claim ambiguous as to whether the clauses which immediately follow are positively recited and required claim limitations
Additionally, each of claims 3 and 9 are indefinite for the following reasons: A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c).
In the present instance, claims 3 and 9 recites broader and narrower recitations of ranges of tangential flow rate, transmembrane pressure, volume of original salt solution and filter pore size, respectively.
The claims are considered indefinite on these grounds because there is a question or doubt as to whether the features introduced by such narrower language is (a) merely exemplary of the remainder of the claims, and therefore not required, or (b) a required features of the claims.
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 1-6 and 8-12 are rejected under 35 U.S.C. 103 as being unpatentable over Delisle et al PGPUBS Document US 2021/0228684 (Delisle) in view of Sutherland et al PGPUBS Document US 2012/0302734 (Sutherland). Referenced paragraph numbers of the applied PGPUBS Documents are identified by “[ ]” symbols referring to the paragraphs immediately preceding the respective “[ ]” symbols.
For independent claim 1, Delisle discloses a method for preparing a controllable high-concentration silk fibroin solution [0006-0007, 0011 and 0093 re producing of a silk fibroin article of up to 99% or greater purity or concentration] by tangential flow membrane filtration technology [0093 and 0097 re “tangential flow filtration”], comprising the following steps:
S1: obtaining an inorganic salt solution of silk fibroin [0078 re processing of silk with the aid of a charotropic agent comprising one or more of varied inorganic salts] and [;
S2: subjecting the inorganic salt solution of silk fibroin to a membrane clarification process [0094 re the processed salt solution undergoing membrane dialysis to remove undesired salts and other contaminants, thus being clarified] ;
S3: performing a desalination process on the inorganic salt solution of silk fibroin: filtering a clarified solution obtained from the membrane clarification process through a tangential flow filtration system [0093 and 0097-0098 re combining process steps of membrane dialysis to remove contaminants and thus clarify the silk solution and tangential flow filtration]; and,
S4: concentrating the silk fibroin solution to obtain an aqueous solution of silk fibroin with a high molecular weight ([0066, 0079, 0080, 0087, 0088 re producing or obtaining silk fibroin solution of higher or high molecular weight, such as by boiling], [0099 re further purification to isolate processed silk of desired molecular weight] and [0116 re chemical or mechanical processing modulation steps to fine tune the MW of the product]).
Claim 1, and claims dependent therefrom, differ from Delisle by requiring the preparation by tangential flow membrane filtration technology to comprise tangential flow ultrafiltration technology.
Sutherland teaches production of a concentrated and purified silk dope product [0001 and 0017-0018] including purifying a salt-containing silk solution by membrane filtration, preferably tangential flow filtration, using a membrane which may be an ultrafiltration or UF membrane filter [0017, 0282-0284 and 0287].
Sutherland suggests in [0283, 0285 and 0287 that employing tangential flow filtration with UF membranes effectively isolates or removes contaminants or constituents having a molecular weight (MW) of 5-300 kDa which are commonly found in silk solutions, and is effective to isolate silk proteins].
Thus, it would have been obvious to one of ordinary skill in the art of processing and purifying silk solutions to have practiced or modified the method disclosed by Delisle, by utilizing a UF type tangential flow membrane in the step of employing a tangential flow membrane, as taught by Sutherland, so as to isolate or removes contaminants or constituents having a molecular weight (MW) of 5-300 kDa which are commonly found in silk solutions, and also effective to isolate silk proteins, so as to produce additional commercially valuable silk protein byproducts in addition to production of silk fibroin.
For claim 2, Delisle further teaches that, in step S3, filtration in the desalination process is performed through an ultrafiltration system, which is a tangential flow filtration system; the tangential flow filtration system comprising a membrane module as a filtration component.
Sutherland further teaches silk product processing to employ membrane modules of a filtration material such as polyethersulfone, regenerated cellulose, or polyacrylonitrile; preferably, a material with characteristics such as high flow rate and high flux, natural hydrophilicity, and low adsorption; and most preferably, a regenerated cellulose material [0284 re use of membranes of polyethersulfone or regenerated cellulose, which are readily modified to have desired hydrophobic or hydrophilic characteristics for separating solution components, and inherently having a high flow rate and high flux, natural hydrophilicity, and low adsorption, and having a desirable molecular weight cutoff value]).
It would have been further obvious to the skilled artisan to have utilized such membrane material taught by Sutherland in the Delisle method, so as utilize membrane material which is readily modified to have desired hydrophobic or hydrophilic characteristics for separating solution components, and inherently having a high flow rate and high flux, natural hydrophilicity, and low adsorption, and a desirable molecular weight cutoff value.
For claim 3, Delisle is silent regarding specific flow rates and achieved transmembrane pressures present in step S3, when filtering the clarified solution obtained from the membrane clarification process through the tangential flow filtration system, and does not explicitly disclose that the tangential flow rate is 0-60 L/min/m.sup.2, preferably 1-50 L/min/m.sup.2, 2-40 L/min/m.sup.2, 3-30 L/min/m.sup.2, or 4-20 L/min/m.sup.2, and more preferably 5-10 L/min/m.sup.2; nor explicitly disclose that the transmembrane pressure is 0.001-3.0 bar, preferably 0.01-2.5 bar, 0.1-2.0 bar, and more preferably 0.15-1.5 bar, such as 0.2-1.0 bar.
However, Delisle does suggest such relatively low flow rates and pressures in [0097 concerning utilization of controlled peristaltic pumps to effect positive pressures and flow along the membrane surfaces, peristaltic pumps being inherently readily automatically controlled to achieve selected relatively low flow rates and pressures of flow through tangential flow filters.
Delisle is also silent as to the method step of wherein purified water is added to gradually replace the solvent in the silk fibroin solution, with the volume of the purified water added being 1-10 times the volume of the original salt solution, such as 2-8 times the volume of the original salt solution, preferably 3-7 times the volume of the original salt solution or 4-6 times the volume of the original salt solution, and more preferably 5 times the volume of the original salt solution.
However, Delisle also suggests such water replacement mechanism in [0093-0095 regarding TFF being combined with automated dialysis having an automated water change system to purify larger volumes of solution with greater efficiency and programmed multiple changes of solution or buffer].
For claim 4, Delisle futher discloses that, in step S1, the inorganic salt solution of silk fibroin refers to an inorganic salt solution of silk fibroin with a number-average molecular weight of 80 kDa or greater, and preferably, the inorganic salt solution of silk fibroin refers to an inorganic salt solution of silk fibroin with a number-average molecular weight of 80 kDa-200 kDa [0080 re molecular weight of silk fibroin preparations encompassing the claimed ranges].
For claim 5, Delisle further discloses wherein the inorganic salt solution of silk fibroin has a concentration of 0.1-50 wt %, preferably 1-40 wt %, more preferably 2-30 wt %, even more preferably 3-20 wt %, and most preferably 4-10 wt % [0187-0188 re widely varying silk solution concentrations encompassing the claimed concentration ranges].
For claim 6, Delisle further discloses that the inorganic salt is selected from lithium bromide, sodium thiocyanate, lithium thiocyanate, etc [0143 re silk fibroin solutions comprising salts of any of lithium bromide, sodium thiocyanate, lithium thiocyanate].
For claim 8, Delisle further teaches that, in step S3, filtration in the desalination process is performed through an ultrafiltration system, which is a tangential flow filtration system; the tangential flow filtration system comprising a membrane module as a filtration component.
Sutherland further teaches silk product processing to employ membrane modules of a filtration material such as multilayer glass fiber, a multilayer filament polypropylene, functionalized polyethersulfone, or functionalized regenerated cellulose; preferably, a material with characteristics such as a strong clarification capacity, high dirt-holding capacity, high total flux, broad chemical compatibility and low non-specific adsorption; and most preferably, a multilayer glass fiber [0284 re use of membranes of polyethersulfone or regenerated cellulose, which are readily modified to have desired hydrophobic or hydrophilic characteristics for separating solution components, and inherently having a high flux, and low adsorption, and having a desirable molecular weight cutoff value]).
It would have been further obvious to the skilled artisan to have utilized such membrane material taught by Sutherland in the Delisle method, so as utilize membrane material which is readily modified to have desired hydrophobic or hydrophilic characteristics for separating solution components, and have a high total flux, and low non-specific adsorption.
For claim 9, Delisle further discloses that in step S2, the process conditions for the membrane clarification process comprise: pumping the solution into the filter with a filtration area of greater than 10 cm.sup.2 and a pore size of 0.1-50 μm, preferably 0.2-40 μm, 0.5-30 μm or 1-10 μm, more preferably 1-5 μm, and even more preferably 1-2 μm
(Delisle discloses such pumping step in [0097 concerning utilization of controlled peristaltic pumps to effect positive pressures and flow along the membrane surfaces of tangential flow membrane filters], and is silent as to filtration area of filter utilizes, however also suggests that volume of the silk material being filtered may vary widely in [0123 which discusses fractionating processed silk at any scale, ranging from milligrams to kilograms, thus suggesting a similar variation in filter area of filter(s) employed]).
Additionally, such filtatration area ranges are deemed to constitute results-effective variables for which it would have been obvious for one of ordinary skill in the prior art to have optimized by routine experimentation, so as to modify the various processing method steps so as to optimize the production of filtered end product to the scale required by a particular application of the resulting silk product.
The MPEP, Section 2144.05 includes court rulings that have determined that such types of parameter values or ranges do not support the patentability of such subject matter, particularly where the prior art contains similar ranges, amounts or proportions, or suggests such similarity, absent a finding of unexpected criticality or achieving of unexpected results.
For claim 10, Delisle further discloses that, in step S4, the obtained aqueous solution of silk fibroin with high molecular weight refers to an aqueous solution of silk fibroin with a number-average molecular weight of 80 kDa or greater, and preferably, an aqueous solution of silk fibroin with a number-average molecular weight of 80 kDa-200 kDa [0080 re molecular weight of silk fibroin preparations encompassing the claimed ranges].
For claim 11, Delisle further discloses or suggests wherein the number-average molecular weights of the inorganic salt solution of silk fibroin in S1 and the aqueous solution of silk fibroin in S4 are measured by a rheological method [0174 re determination of formulations being optimized to modulate rheological properties] .
For claim 12, Delisle discloses or suggests wherein in step S4, the obtained aqueous solution of silk fibroin with high molecular weight has a mass fraction of 1-40 wt %, preferably a mass fraction of 2-30 wt %, more preferably 3-20 wt %, and even more preferably 4%-10 wt %; the mass fraction is the ratio of the mass of silk fibroin to the mass of aqueous solution of silk fibroin [0080 regarding widely varying optional ranges of achieved high molecular weights of the solution, inherently encompassing and overlapping meeting the claimed high molecular weight mass fractions or mass fraction proportions].
Additionally, such mass fraction ratio ranges are deemed to constitute results-effective variables for which it would have been obvious for one of ordinary skill in the prior art to have optimized by routine experimentation, so as to modify the various processing method steps so as to vary the MW and also mass fraction proportions of the silk fibroin, in order to tailor the resulting silk fibroin product to particular product applications. The MPEP, Section 2144.05 includes court rulings that have determined that such types of parameter values or ranges do not support the patentability of such subject matter, particularly where the prior art contains similar ranges, amounts or proportions, or suggests such similarity, absent a finding of unexpected criticality or achieving of unexpected results.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Delisle et al PGPUBS Document US 2021/0228684 (Delisle) in view of Sutherland et al PGPUBS Document US 2012/0302734 (Sutherland), as applied to claims 1-6 and 8-12 above, and further in view of Leisk et al PGPUBS Document US 2019/0001272 (Leisk).
Referenced paragraph numbers of the applied PGPUBS Documents are identified by “[ ]” symbols referring to the paragraphs immediately preceding the respective “[ ]” symbols.
For claim 7, Delise further discloses in the method for acquiring the inorganic salt solution of silk fibroin, the following steps: S11:
degumming, washing, and drying steps including :
mixing silkworm cocoons with a carbonate and water, and
heating the mixture to obtain a degummed silk; and
washing and drying the degummed silk (all taught in [0059 and 0060 re mixing silkworm cocoons with boiling water, heating, degumming, rinsing, i.e. “washing”], in [0061 re addition of sodium carbonate, alkaline solutions] and in [0062-0064 re boiling, thus removing water by vaporizing and thus drying the degummed silk]).
Claim 7 further differs from Delise by requiring a step of Step of S12, comprising:
a dissolution step:
dissolving the dried and degummed silk obtained from S11 in an inorganic salt solution, and
heating to give the inorganic salt solution of silk fibroin with a high salt concentration.
Leisk teaches a method for processing, purifying and concentrating salt-containing silk fibroin solutions (Abstract and [0008-0012], the purifying comprising passing the solution through a porous membrane [0021-0028], the membrane comprising a tangential flow filtration membrane [0157, 0280-0281].
Leisk also teaches processing steps including such degumming, washing, and drying steps including : mixing silkworm cocoons with carbonate and water, heating the mixture to obtain a degummed silk; and washing and drying the degummed silk [0119, 0134-0137]; as well as the additional steps of: dissolution [0142-0143 re squeezing out and drying the degummed silk, dissolving of extracted, dried silk fibroin in an inorganic salt-containing aqueous solution] and [0144 re heating of such dissolved silk for up to about 4 hours].
Leisk teaches that such additional processing steps result in tailoring of the silk solution product viscosity [0145].
It would have been additionally obvious to the skilled artisan to have also modified the Delise method by including the additional processing steps taught by Leisk, in order to more finely tailor the silk solution product viscosity.
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Of particular interest ,
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Primary Examiner Joseph Drodge at his direct government formal facsimile phone number telephone number of 571-272-1140. The examiner can normally be reached on Monday-Friday from approximately 8:00 AM to 1:00PM and 2:30 PM to 5:30 PM.
If attempts to reach the examiner are unsuccessful, the examiner' s supervisor, Benjamin Lebron, of Technology Center Unit 1773, can reached at 571-272-0475.
The telephone number, for official, formal communications, for the examining group where this application is assigned is 571-273-8300.
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JWD
03/20/2026
/JOSEPH W DRODGE/ Primary Examiner, Art Unit 1773