DETAILED CORRESPONDENCE
Status of the Application
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant’s submission filed on 11/17/2025 has been entered.
Claims 1, 3-15, 28-29, and 31-34 are pending in this application.
Applicant’s amendment to the claims filed 11/17/2025 is acknowledged. This listing of the claims replaces all prior versions and listings of the claims.
Applicant’s remarks filed on 11/17/2025 in response to the final rejection mailed on 07/24/2025 is acknowledged and has been fully considered.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112(b)
The rejection of claims 1, 3-15, 28-31 and 33 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point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention is withdrawn in view of
the amendment to claim 1 to recite “the basic medium containing water is from 40 °C to 180 °C”, and
the amendment to claim 15 to recite “bringing a raw material composition containing an esterified protein and a base into contact with water vapor”.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 3-4, 6, 10 and 31 under 35 U.S.C. 103 as being unpatentable over Ueda et al. (US Patent No. 7,186,806; cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Ueda) in view of Zheng et al. (Proteomics Sys Biol, 2016, 16:1059; cited on the Form PTO-892 mailed 11/13/2024; herein referred to as Zheng) and evidentiary references Shoulders et al. (Ann Rev Biochem, 2009, 78:929-958; cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Shoulders) and Zeeman et al. (Biomaterials, 1999, 20:921-931; cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Zeeman),
the rejection of claim 5 under 35 U.S.C. 103 as being unpatentable cover Ueda in view of Zheng, and further in view of Yamashita et al. (JPH10298201A; cited on Form PTO-892 mailed on 11/21/2023; reference is made to a machine translation cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Yamashita),
the rejection of claims 7, 9, 13, 30 and 33 under 35 U.S.C. 103 as being unpatentable over Yamashita, Zheng and Ueda in view of Zheng, and further in view of Sutti et al. (US 2014/0264985; cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Sutti),
the rejection of claims 8 and 32 under 35 U.S.C. 103 as being unpatentable over Ueda in view of Zheng and Sutti, and further in view of Lee et al. (Phys Chem Phys, 2016, 18:4814-4821; cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Lee),
the rejection of claim 11 under 35 U.S.C. 103 as being unpatentable over Ueda in view of Zheng, and further in view of Brand et al. (Textile Res J, 1962, 32(1):39-49; cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Brand),
the rejection of claims 12 and 29 under 35 U.S.C. 103 as being unpatentable over Ueda in view of Zheng, and further in view of Hormann et al. (Biochem, 1971, 10:932; cited on the attached Form PTO-892; herein referred to as Hormann) and evidentiary reference Cavallaro et al. (Biotechnol Bioeng, 1994, 43:781; cited on the attached Form PTO-892; herein referred to as Cavallaro),
the rejection of claim 14 under 35 U.S.C. 103 as being unpatentable over Ueda in view of Zheng and Sutti, and further in view of Lo et al. (US 2015/0183841; cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Lo), and
the rejection of claims 15 and 28 under 35 U.S.C. 103 as being unpatentable over Ueda in view of Zheng, and further in view of Hu et al. (Biomacromolecules, 2011, 12(5):1686-1696; cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Hu) and evidentiary reference Zeeman,
are withdrawn in view of the amendment to claims 1 and 32 to recite “hydrolyzing an ester group by bringing a raw material composition containing an esterified protein into contact with a basic medium”, and the amendment to claim 15 to recite “hydrolyzing an ester group by bringing a raw material composition containing an esterified protein into contact with a base”.
Claims 1, 3-6, 10 and 31 are newly rejected under 35 U.S.C. 103 as being unpatentable over Yamashita in view of Zheng and Stefanidis et al. (JACS, 1993, 115:6045; cited on the attached Form PTO-892; herein referred to as Stefanidis), and evidentiary reference Laidler et al. (J Chem Ed, 1984, 61:494; cited on the attached Form PTO-892; herein referred to as Laidler).
Claim 1 is drawn to a method of producing a protein composition involving hydrolyzing an ester group by bringing a raw material composition containing an esterified protein into contact with a basic medium, wherein the esterified protein contains:
a formic acid ester formed by a reaction of formic acid with a hydroxyl group in the esterified protein, or
an acetic acid ester formed by a reaction of acetic acid with a hydroxyl group in the esterified protein, and
wherein the basic medium contains water, and the basic medium containing water is from 40 °C to 180 °C.
Yamashita relates to the treatment of cellulose esters generated by treatment with organic acids [abstract of the translation].
Regarding the limitation of bringing a raw material composition containing an esterified protein into contact with a basic medium in claim 1 and the limitations of claim 5, Yamashita teaches a method of preparing a cellulose ester by contacting cellulose with an organic acid [p 3, top paragraph], and treating the cellulose ester with an alkali (such as ammonia) wherein the liquid phase of the wet fibrillated cellulose ester is adjusted to pH of 5-9 [abstract] in order to suppress corrosion and acid odors resulting from ester hydrolysis [para 0004 of the translation]. Yamashita teaches that esters stored over a long period of time can become hydrolyzed and release free acid as a result, wherein the hydrogen ion of the free acid catalyzes more ester hydrolysis, and therefore adding alkali such as ammonia, NaOH and KOH would lower the hydrogen ion concentration and suppress the amount of free acid generated [p 5, section “Alkali Treatment Step”], therein limiting the free acid odors resulting from such hydrolysis in long-term storage [abstract]. Therefore Yamashita teaches a step of treating an esterified protein with a basic medium.
Stefanidis discusses general base catalysis of ester hydrolysis [title], and discloses that bases can bring about hydrolysis of esters by nucleophilic catalysis and by general base catalysis, wherein general base catalysis occurs by removing a proton from water for an attack on an acyl compound [p 6045, col 1, paras 1-2], and shows increasing rate of hydrolysis (kobs) with increasing base on formate esters in [Figure 1]. In view of Stefanidis, one of skill in the art would recognize that the treatment of an ester with a base as taught by Yamashita would still result in ester hydrolysis through general base catalysis, and also that said general base catalysis would not produce a free acid, thereby accomplishing the goal of Yamashita to prevent formation of free acid over time. Therefore the treatment of an esterified protein with an alkali as taught by Yamashita is considered to correspond to the step of contacting an esterified protein with a basic medium that results in ester hydrolysis.
Regarding the limitation of the basic medium between 40 °C to 180 °C in claim 1 and the limitation of between 40 °C and the boiling point in claim 4, Yamashita teaches the cellulose ester solution is about 0 to 60 °C to facilitate the precipitation into a fibrous form [p 4, 4th paragraph]. While Yamashita does not explicitly teach a basic medium between 40 °C to 180 °C (or the boiling point corresponding to claim 4), without any teaching to suggest otherwise, one of ordinary skill in the art would have reasonably expected to maintain the temperature of reactions throughout the method of Yamashita. Considering an alternative interpretation that Yamashita suggests altering temperature through the lack of an explicit teaching of a temperature for ester hydrolysis, the teachings of Stefanidis correspond to the hydrolysis of organic acid esters at 25 °C [p 6045, col 2, para 2], and according to MPEP 2144.05.II.A, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. As Stefanidis teaches the base hydrolysis of organic acid esters at 25 °C, one of skill in the art would have been motivated to increase the temperature to the claimed range in order to increase the rate of ester hydrolysis for a more efficient hydrolysis reaction, as reaction rate and temperature are understood to be directly related in chemical reactions as evidenced by Laidler [p 494, col 1, beginning at final paragraph].
Yamashita does not teach an esterified protein containing a formic acid ester formed by a reaction of formic acid with a hydroxyl group in the protein, or an acetic acid ester formed by a reaction of acetic acid with a hydroxyl group in the protein.
Zheng discusses the O--formylation of proteins incubated in concentrated formic acid [title], and discusses that formic acid is among the most effective solvents for protein solubilization that can disrupt intramolecular hydrogen bonds to solvate polar amino acid residues, and has been employed to solubilize milk casein, wool keratin, collagen and silk proteins [p 1059, col 1, para 1].
Regarding the limitation of a protein containing a formic acid ester in claim 1, Zheng teaches that the primary reaction product of formic acid with protein is O-formylation of Ser and Thr residues [p 1060, “Significance of the Study” section], which corresponds to the formation of a formic acid ester through the reaction of formic acid with a hydroxyl group in the protein [p 1060, col 1, para 1]. Zheng further teaches that this covalent modification of proteins is unfortunate as it can disrupt downstream applications such as Mass Spectrometry [p 1060, “Significance of the Study” section], therefore suggesting that formic acid addition bestows many benefits to protein solubilization that may require steps to address the O-formylation of proteins depending on the desired application.
While Yamashita discusses cellulose esters formed by the addition of an organic acid to cellulose, the ester bonds formed and their subsequent hydrolysis are considered relevant to the O-formylated proteins of Zheng, as each of the esters of Zheng and Yamashita are understood to occur at the hydroxyl groups of the respective substrates (cellulose for Yamashita, and Ser/Thr residues of proteins such as collagen for Zheng), and as such, each esterified product would be expected to undergo base hydrolysis as taught by Stefanidis, as each esterified product contains an acyl group by definition.
In view of Yamashita, Zheng and Stefanidis, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Yamashita by using an O-formylated collagen ester, as taught by Zheng, to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the O-formylated collagen of Zheng and the cellulose organic acid ester of Yamashita are both organic acid esters, and as such both are capable of being incorporated into such methods as described by Yamashita and Stefanidis. Thus it would have been obvious to one of ordinary skill in the art to replace the cellulose organic acid ester of Yamashita with the O-formylated collagen of Zheng, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the Yamashita and Zheng discuss methods of esterifying and hydroxyl containing substrates with organic acids, and Yamashita and Stefanidis discuss methods of contacting an organic acid with a base.
Regarding claim 3, Yamashita teaches the use of NaOH as the alkali, which is considered to correspond to an aqueous solution [p 5, section “Alkali Treatment Step”].
Regarding claim 6, Zheng teaches formic acid is among the most effective solvents for protein solubilization that can disrupt intramolecular hydrogen bonds to solvate polar amino acid residues, and has been employed to solubilize milk casein, wool keratin, collagen and silk proteins [p 1059, col 1, para 1], wherein collagen is understood to be a structural protein.
Regarding claims 10 and 31, Yamashita teaches the method of preparing esters for fibers and the formation of a fibril cellulose ester [para 0001].
Therefore, the invention of claims 1, 3-6, 10 and 31 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 7, 9, 13 and 33 are newly rejected under 35 U.S.C. 103 as being unpatentable over Yamashita, Zheng and Stefanidis as applied to claims 1, 3-6, 10 and 31 above, and further in view of Sutti et al. (US 2014/0264985; cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Sutti).
Claim 7 is drawn to the method of claim 6, wherein the structural protein comprises fibroin.
The teachings of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-6, 10 and 31 are discussed above. These references do not teach that the structural protein is fibroin.
Sutti discusses fibers and fiber forming processes [title] that include production methods to overcome the common disadvantages in the field regarding difficulties purifying and isolating formed fibers [para 0004].
Regarding claims 7 and 9, Sutti teaches an embodiment wherein “the fibre-forming liquid may include at least one polymer selected from the group consisting of polypeptides, alginates, chitosan, starch, collagen, silk fibroin, polyurethanes, polyacrylic acid, polyacrylates, polyacrylamides, polyesters, polyolefins, boronic acid functionalised polymers, polyvinylalcohol, polyallylamine, polyethyleneimine, poly(vinyl pyrrolidone), poly(lactic acid), polyether sulfone and inorganic polymers” [para 0030]. As Zheng discusses methods of using formic acid for solubilizing structural proteins such as silk proteins that correspond to silk fibroin that results in unfortunate O-formylation of proteins, and Yamashita and Stefanidis teach methods of hydrolyzing organic acid esters, one of skill in the art would be motivated to utilize the combined method of Yamashita, Zheng and Stefanidis on silk fibroin to increase its solubility and subsequently remove any resulting formic acid esters for greater success with downstream applications as taught by Zheng.
In view of Sutti, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Yamashita, Zheng and Stefanidis by using silk fibroin, as taught by Sutti, to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that both silk fibroin and collagen are structural proteins commonly used for fiber production as taught by Sutti, and as such, both are capable of being modified as formic acid esterified proteins as taught by Zheng, and subsequently hydrolyzed as taught by Yamashita and Stefanidis. Thus it would have been obvious to one of ordinary skill in the art to replace collagen with silk fibroin, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because Sutti relates to industrial fiber formation processes using structural proteins such as silk fibroin and collagen, and Zheng relates to solubilization of structural proteins such as collagen and silk proteins for greater success with their downstream applications.
Regarding claim 13, Sutti teaches electrospinning to produce a continuous polymer fiber with controllable diameter, composition and fiber orientation [para 0002]. While hank is not defined by the instant application, the term is known in the art as a unit of loose assemblage of fibers forming a single strand. Therefore the methods of Sutti satisfy the limitations of claim 13.
Regarding claim 33, Sutti teaches methods to overcome the common disadvantages in the field regarding difficulties purifying and isolating formed fibers [para 0004] that include silk fibroin [para 0030]. In view of the combined method of Yamashita, Zheng, Stefanidis and Sutti as discussed above, the use of silk fibroin corresponds to an esterified protein that is not esterified collagen.
Therefore, the invention of claims 7, 9, 13 and 33 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 8 and 32 are newly rejected under 35 U.S.C. 103 as being unpatentable over Yamashita, Zheng, Stefanidis and Sutti as applied to claims 1, 3-7, 9-10, 13, 31 and 33 above, and further in view of Lee et al. (Phys Chem Phys, 2016, 18:4814-4821; cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Lee).
Claim 8 is drawn to the method of claim 7, wherein the fibroin comprises spider silk fibroin.
The combined teachings of Yamashita, Zheng, Stefanidis and Sutti as applied to claims 1, 3-7, 9-10, 13, 31 and 33 are discussed above. These references do not teach that the fibroin is spider silk fibroin.
Lee discusses comparisons between fibroin from spiders and silkworms [abstract], as silk fibers from both organisms can be used to produce materials with mechanical characteristics similar to advance synthetic polyamide fibers in terms of their strength and fracture toughness [p 4814, para 1].
Regarding claims 8 and 32, Lee teaches that "silkworm fibroin displayed less flexibility and greater stiffness relative to the spider fibroin" [p 4817, col 1, para 2] and that both silks form beta-sheet structures [p 4819, col 1, para 2].
In view of Lee, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Yamashita, Zheng, Stefanidis and Sutti, by using spider silk fibroin, as taught by Lee, to arrive at the claimed invention. One of ordinary skill in the art would have recognized that silk fibroin sourced from both silkworms and spiders contains a comparable beta-sheet structure with comparable mechanical advantages when used for fiber-formation, wherein spider silk fibroin bears comparatively more flexibility as taught by Lee. Thus, it would have been obvious to one of ordinary skill in the art to use silk fibroin sourced from spiders, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success since both Sutti discusses industrial fiber formation processes using silk fibroin, and Lee discusses the mechanical comparisons between different types of fibroin that are commonly used for industrial fiber-formation and acknowledges that both silks from both silkworms and spiders form beta-sheet structures.
Therefore, the invention of claims 8 and 32 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 11 is newly rejected under 35 U.S.C. 103 as being unpatentable over Yamashita, Zheng and Stefanidis as applied to claims 1, 3-6, 10 and 31 above, and further in view of Brand et al. (Textile Res J, 1962, 32(1):39-49; cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Brand).
Claim 11 is drawn to the method of claim 1, wherein the raw material composition comprises a fiber, the medium containing water is an aqueous solution, and the production method further comprises a crimping step of crimping the fiber by bringing the fiber into contact with the aqueous solution.
The teachings of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-6, 10 and 31 are discussed above. These references do not teach the process of crimping by bringing fiber into contact with an aqueous solution.
Brand discusses the mathematical principles of fiber crimp (title), including the contribution of fiber crimp to the final characteristics of the finished fabric [p 39, para 1].
Regarding claim 11, Brand teaches mathematical formulas relating the change in crimp of wool fibers and states "Q [is] the change in the spatial form of the crimp of a fiber when we change conditions such as temperature, humidity, etc." [p 41, col 1, para 2].
In view of Brand, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Yamashita, Zheng and Stefanidis by adding a crimping step, as taught by Brand, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Yamashita, Zheng and Stefanidis by adding a crimping step, because Brand teaches that percentage of crimp in a fiber is related to its exposure to humidity, and therefore water in an aqueous solution, and the degree of crimp in a fiber contributes to the characteristics of the final fabric. One of ordinary skill in the art would have had a reasonable expectation of success because Yamashita discusses a method of generating fibers, and Brand describes the mathematical relationships for determining physical characteristics of fibers.
Therefore, the invention of claim 11 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 12 and 29 are newly rejected under 35 U.S.C. 103 as being unpatentable over Yamashita, Zheng and Stefanidis as applied to claims 1, 3-6, 10 and 31 above, and further in view of Hormann et al. (Biochem, 1971, 10:932; cited on the attached Form PTO-892; herein referred to as Hormann) and evidentiary reference Cavallaro et al. (Biotechnol Bioeng, 1994, 43:781; cited on the attached Form PTO-892; herein referred to as Cavallaro).
Claim 12 is drawn to the production composition of claim 1, wherein the raw material composition comprises a fiber, the basic medium containing water is a basic aqueous solution, and the production method further comprises a shrink-proof step of bringing the fiber into contact with the aqueous solution.
The teachings of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-6, 10 and 31 are discussed above. These references do not teach the process of shrink-proofing by bringing fiber into contact with an aqueous solution.
Hormann discusses reversible and irreversible denaturation of collagen fibers [title], and describes that native fibers shrink to about one-third of their original length when heated in water above 62 °C due to the denaturation of covalently cross-linked collagen molecules that transform the triple-helix structure to randomly coiled peptide chains [p 932, col 1, para 1], which can affect the mechanical properties of collagen as they are dependent on the degree of covalent crosslinking as evidenced by Cavallaro [p 785, col 2, para 2].
Regarding claim 12, Hormann teaches that denaturation (and therefore shrinkage) of collagen proceeds at a temperature below the shrinkage temperature given time, but only to a limiting value, as stabilizing lattice forces within the collagen fiber limit the progress to denaturation [p 937, col 1, para 2] as shown in by the treatment of collagen fibers of rattail tendons in water [Figure 4]. Hormann further teaches considerable renaturation and restoration of triple helix structure can be achieved at 20-30 °C following denaturation, wherein original lattice structure restoration is further promoted by stretching the fibers [p 937, col 1, paras 4-6]. Therefore one of skill in the art would be able to use the teachings of Hormann to prevent shrinkage by contacting the fiber with water below the denaturation temperature of collagen, and could subsequently rescue the fiber from shrinkage by further cold storage of the fiber in water.
In view of Hormann, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Yamashita, Zheng and Stefanidis by adding a shrink-proofing step, as taught by Hormann, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Yamashita, Zheng and Stefanidis, because Hormann teaches methods to both reduce and reverse the shrinkage of collagen fibers by preventing denaturation and promoting renaturation that affects the mechanical properties of the fibers. One of ordinary skill in the art would have had a reasonable expectation of success because Zheng relates to the esterification of collagen for greater success with their downstream applications, and Hormann describes strategies to maintain the structure of downstream materials formed by collagen.
Regarding claim 29, Hormann does not teach a protein fiber with a shrinkage rate of -5% to +5% as defined by Equation 1. Hormann however does teach a method of reducing shrinkage of collagen and restoring shrinkage of collagen [p 937, col 1, para 2; p 937, col 1, paras 4-6]. According to MPEP 2144.05.II.A, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum workable ranges by routine experimentation. One of skill in the art would have been motivated apply the principles of Hormann to control protein fiber shrink rate, and would have had a reasonable expectation of success as Hormann discloses a range of temperatures and times to both prevent and restore shrinkage of collagen [Figures 4-6] before the effective filing date.
Therefore, the invention of claims 12 and 29 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 14 is newly rejected under 35 U.S.C. 103 as being unpatentable over Yamashita, Zheng and Stefanidis as applied to claims 1, 3-6, 10 and 31 above, and further in view of Lo et al. (US 2015/0183841; cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Lo).
Claim 14 is drawn to the method of claim 10, wherein the raw material composition comprises a fiber, and the fiber is in a cloth state.
The combined teachings of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-6, 10 and 31 are discussed above. These references do not teach that the fiber is in a cloth state.
Lo discusses the uses of high molecular weight silk fibroin [title].
Regarding claim 14, According to MPEP 2144.04.IV.C, selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Lo teaches that silk fibroin from the silkworm Bombyx mori is a material that has been used as a cloth (p 0004), and that silk-based materials such as these have biomedical applications to produce high strength materials. As such, the silk fiber in cloth state still contains the same functional groups for the esterification and ester hydrolysis reactions as set forth in the prior art.
In view of Lo, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Yamashita, Zheng and Stefanidis by treating silk fibroin cloth, as taught by Lo, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Yamashita, Zheng and Stefanidis to treat silk cloth, because Lo teaches that silk fibers can be used as cloth for biomedical applications, and the fiber in cloth state still bears the same functional groups for the esterification and ester hydrolysis reactions. One of ordinary skill in the art would have had a reasonable expectation of success because Yamashita discusses a fiber formation process from an esterified cellulose, Zheng discusses solubilization of structural proteins such as collagen and silk by esterification for greater success with their downstream applications, and Lo describes different fibers made from structural proteins and their downstream applications as cloth materials.
Therefore, the invention of claim 14 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claims 15 and 28 are newly rejected under 35 U.S.C. 103 as being unpatentable over Yamashita, Zheng and Stefanidis as applied to claims 1, 3-6, 10 and 31 above, and further in view of Hu et al. (Biomacromolecules, 2011, 12(5):1686-1696; cited on Form PTO-892 mailed on 11/21/2023; herein referred to as Hu) and evidentiary reference Laidler.
The claims are drawn to a protein production method comprising hydrolyzing an ester group by bringing a raw material composition containing an esterified protein and a base into contact with water vapor, wherein the esterified protein contains:
a formic acid ester formed by a reaction of formic acid with a hydroxyl group in the esterified protein, or
an acetic acid ester formed by a reaction of acetic acid with a hydroxyl group in the esterified protein,
wherein the water vapor is from 40 °C to 180 °C.
Regarding claim 15 and the limitations of hydrolyzing an ester group from an esterified protein with a base, Yamashita teaches a method of preparing a cellulose ester by contacting cellulose with an organic acid [p 3, top paragraph], and treating the cellulose ester with an alkali (such as ammonia) wherein the liquid phase of the wet fibrillated cellulose ester is adjusted to pH of 5-9 [abstract] in order to suppress corrosion and acid odors resulting from ester hydrolysis [para 0004 of the translation]. Yamashita teaches that esters stored over a long period of time can become hydrolyzed and release free acid as a result, wherein the hydrogen ion of the free acid catalyzes more ester hydrolysis, and therefore adding alkali such as ammonia, NaOH and KOH would lower the hydrogen ion concentration and suppress the amount of free acid generated [p 5, section “Alkali Treatment Step”], therein limiting the free acid odors resulting from such hydrolysis in long-term storage [abstract]. Therefore Yamashita teaches a step of treating an esterified protein with a basic medium.
Stefanidis discusses general base catalysis of ester hydrolysis [title], and discloses that bases can bring about hydrolysis of esters by nucleophilic catalysis and by general base catalysis, wherein general base catalysis occurs by removing a proton from water for an attack on an acyl compound [p 6045, col 1, paras 1-2], and shows increasing rate of hydrolysis (kobs) with increasing base on formate esters in [Figure 1]. In view of Stefanidis, one of skill in the art would recognize that the treatment of an ester with a base as taught by Yamashita would still result in ester hydrolysis through general base catalysis, and also that said general base catalysis would not produce a free acid, thereby accomplishing the goal of Yamashita to prevent formation of free acid over time. Therefore the treatment of an esterified protein with an alkali as taught by Yamashita is considered to correspond to the step of contacting an esterified protein with a basic medium that results in ester hydrolysis.
Regarding claim 15 and the limitation of the basic medium between 40 °C to 180 °C, Yamashita teaches the cellulose ester solution is about 0 to 60 °C to facilitate the precipitation into a fibrous form [p 4, 4th paragraph]. While Yamashita does not explicitly teach a basic medium between 40 °C to 180 °C (or the boiling point corresponding to claim 4), without any teaching to suggest otherwise one of skill in the art would be reasonably expected to maintain the temperature of reactions throughout the method of Yamashita. Considering an alternative interpretation that Yamashita suggests altering temperature through the lack of an explicit teaching of a temperature for ester hydrolysis, the teachings of Stefanidis correspond to the hydrolysis of organic acid esters at 25 °C [p 6045, col 2, para 2], and according to MPEP 2144.05.II.A, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. As Stefanidis teaches the base hydrolysis of organic acid esters at 25 °C, one of skill in the art would have been motivated to increase the temperature to the claimed range in order to increase the rate of ester hydrolysis for a more efficient hydrolysis reaction, as reaction rate and temperature are understood to be directly related in chemical reactions as evidenced by Laidler [p 494, col 1, beginning at final paragraph].
Yamashita does not teach an esterified protein containing a formic acid ester formed by a reaction of formic acid with a hydroxyl group in the protein, or an acetic acid ester formed by a reaction of acetic acid with a hydroxyl group in the protein, or the use of water vapor for the hydrolysis reaction.
Zheng discusses the O--formylation of proteins incubated in concentrated formic acid [title], and discusses that formic acid is among the most effective solvents for protein solubilization that can disrupt intramolecular hydrogen bonds to solvate polar amino acid residues, and has been employed to solubilize milk casein, wool keratin, collagen and silk proteins [p 1059, col 1, para 1].
Regarding claim 15 and the limitation of a protein containing a formic acid ester, Zheng teaches that the primary reaction product of formic acid with protein is O-formylation of Ser and Thr residues [p 1060, “Significance of the Study” section], which corresponds to the formation of a formic acid ester through the reaction of formic acid with a hydroxyl group in the protein [p 1060, col 1, para 1]. Zheng further teaches that this covalent modification of proteins is unfortunate as it can disrupt downstream applications such as Mass Spectrometry [p 1060, “Significance of the Study” section], therefore suggesting that formic acid addition bestows many benefits to protein solubilization that may require steps to address the O-formylation of proteins depending on the desired application.
While Yamashita discusses cellulose esters formed by the addition of an organic acid to cellulose, the ester bonds formed and their subsequent hydrolysis are considered to relevant to the O-formylated proteins of Zheng, as each of the esters of Zheng and Yamashita are understood to occur at the hydroxyl groups of the respective substrates (cellulose for Yamashita, and Ser/Thr residues of proteins such as collagen for Zheng), and as such, each esterified product would be expected to undergo base hydrolysis as taught by Stefanidis, as each esterified product contains an acyl group by definition.
Hu discusses methods to obtain refined control of the molecular structure of silk biomaterials through temperature-controlled water vapor annealing or TCWVA [abstract].
Regarding the limitations recited in claims 15 and 28 of using water vapor for the hydrolysis reaction, Hu teaches "a method… to regulate the interaction of proteins and water molecules … can promote protein crystallization during interaction with water molecules but avoid possible dissolution" [p 1687. col 1, para 1], wherein TCWVA is described as "a new physical approach to control the structure of fibrous protein" [p 1687, col 1, para 2] using silk fibroin [p 1687, col 1, para 3] at a variety of temperatures ranging 4 - 100 °C [Table 1].
In view of Yamashita, Zheng and Stefanidis, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Yamashita by using an O-formylated silk protein ester, as taught by Zheng, to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the O-formylated silk protein of Zheng and the cellulose organic acid ester of Yamashita are both organic acid esters, and as such both are capable of being incorporated into such methods as described by Yamashita. Thus it would have been obvious to one of ordinary skill in the art to replace the cellulose organic acid ester of Yamashita with the O-formylated silk protein ester of Zheng, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the Yamashita and Zheng discuss methods of esterifying and hydroxyl containing substrates with organic acids.
In view of Hu, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Yamashita, Zheng and Stefanidis by using water vapor in the hydrolysis reaction, as taught by Hu, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Yamashita, Zheng and Stefanidis by using water vapor in the hydrolysis reaction, because Hu teaches that using the temperature-controlled water vapor annealing method regulates the interaction of protein and water molecules that allows the control of fibrous protein structure. One of ordinary skill in the art would have had a reasonable expectation of success because Zheng discusses the preparation of silk and collagen fibers for downstream processes via esterification, and Hu describes a method to control the structure of fiber proteins during modification reactions.
Therefore, the invention of claims 15 and 28 would have been obvious to one of ordinary skill in the art before the effective filing date.
Claim 34 is newly rejected under 35 U.S.C. 103 as being unpatentable over Yamashita, Zheng, Stefanidis, Sutti and Lee as applied to claims 1, 3-10, 13, and 31-33 above, and further in view of Guinea et al. (J Exp Biol, 2005, 208:25; cited on the attached Form PTO-892; herein referred to as Guinea).
Claim 34 is drawn to the method of claim 32, wherein the spider silk fibroin fibers have a shrinkage rate of -5% to +5% as defined by Equation (1).
The teachings of Yamashita, Zheng, Stefanidis, Sutti and Lee as applied to claims 1, 3-10, 13, and 31-33 are discussed above. These references do not teach the shrinkage rate of spider silk fibroin fibers.
Guinea relates to the stretching of supercontracted fibers [title], and discusses methods of measuring the effect on tensile strength of stretching silk fibers in an aqueous environment [abstract].
Regarding claim 34, Guinea teaches spider silk fibers are known to undergo supercontraction if unrestrained in water resulting in 50% shrinkage of its initial length and a dramatic change in mechanical behavior [p 25, col 2, para 2], and describes a method of applying force to the spider silk fibers to achieve a desired length in [Figure 2], wherein fiber length is shown to be doubled from the supercontracted state upon stretching corresponding to approximately the original length of the fiber before supercontraction, which is considered to correspond to the shrinkage rate limitations of the claim. Guinea further teaches the stretching corresponds to better alignment of the protein chains resulting in increased stiffness [p 28, col 1, para 2], that the stretching and drying process enables production of spider silk fibers with a tailored and pre-established stress-strain profile in a reliable and repetitive way, and offers the possibility of reproducing the full range of tensile properties exhibited by spider silk fibers [p 28, col 2, beginning at para 3].
In view of Guinea, it would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of Yamashita, Zheng, Stefanidis, Sutti and Lee by adding a step to stretch the spider silk fiber, as taught by Guinea, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of Yamashita, Zheng, Stefanidis, Sutti and Lee, because Guinea teaches the stretching and drying process enables production of spider silk fibers with a tailored and pre-established stress-strain profile in a reliable and repetitive way, and offers the possibility of reproducing the full range of tensile properties exhibited by spider silk fibers. One of ordinary skill in the art would have had a reasonable expectation of success because Sutti discusses industrial fiber formation processes using silk fibroin, Lee discusses the mechanical comparisons between different types of fibroin that are commonly used for industrial fiber-formation and acknowledges that both silks from both silkworms and spiders form beta-sheet structures, and Guinea discusses methods of modulating spider silk fiber shrinkage to tune the stress-strain profile of spider silk fibers.
Therefore, the invention of claim 34 would have been obvious to one of ordinary skill in the art before the effective filing date.
Response to Remarks. Beginning on page 7 of Applicant’s response to the rejections under 35 U.S.C. 103; Applicant in summary contends Ueda appears to describe the hydrolysis of peptide bonds in sodium hydroxide and not the hydrolysis of ester groups, and that Ueda does not disclose the subject matter of claims 1, 15, or 32; Applicant further contends that Yamashita does not remedy the deficiencies of Ueda, as Yamashita teaches away from, discourages, and is directly contrary to conducting hydrolysis through treatment with alkali.
Applicant’s remarks are considered and found not convincing. Regarding the disclosure of Ueda, the rejections of record do not include the teachings of Ueda, and therefore Applicant’s remarks are considered not currently relevant.
Regarding the assertion that Yamashita teaches away from, discourages, and is directly contrary to conducting hydrolysis through treatment with alkali, Yamashita teaches a method of treating an organic acid ester with an alkali to remove the odors caused by free acid, wherein said free acid is produced through the hydrolysis of wet-fibril cellulose esters in storage. Yamashita teaches to add alkali in order to reduce the amount of hydrogen ion, therefore suppressing the amount of acid-catalyzed ester hydrolysis to ultimately prevent the formation of free acid that causes the odor. As shown by Stefanidis, organic acid esters can be hydrolyzed by base through general base catalysis on the acyl group of the ester, which is understood to not produce free acid as a by-product as established by Yamashita. Therefore, in view of Stefanidis, one of ordinary skill in the art would recognize that the treatment of an ester with a base as taught by Yamashita would still result in ester hydrolysis through general base catalysis, and also that said general base catalysis would not produce a free acid, thereby accomplishing the goal of Yamashita to prevent formation of free acid over time and reduce the odor of long term stored esters. Considering that Yamashita does not contend to halt hydrolysis through the addition of the base, and explicitly states that (1) the addition of base would suppress the generated free acid to a small amount to indicate such, and (2) the purpose of the alkali addition is to reduce the odor produced by the resulting free acid, Yamashita is therefore not considered to teach away from, discourage, and be directly contrary to conducting hydrolysis through treatment with alkali, as one of skill in the art would recognize that the addition of base to an organic acid ester will result in ester hydrolysis as indicated by Stefanidis.
Additionally, it is noted that the only active step recited in the claimed method is the contacting of an ester with a base and the intended result of ester hydrolysis, wherein Yamashita teaches the contacting of an ester with a base, and Stefanidis teaches that this will result in ester hydrolysis.
Double Patenting
The provisional rejections as set forth at pp. 25-38 of the previous office action are withdrawn in view of the amendments to claims 1 and 32 to recite “hydrolyzing an ester group by bringing a raw material composition containing an esterified protein into contact with a basic medium”, and the amendment to claim 15 to recite “hydrolyzing an ester group by bringing a raw material composition containing an esterified protein into contact with a base”.
Claims 1, 3-10 and 31-33 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-9 of copending Application No. 17/764669 (herein referred to as “reference application”) in view of Yamashita, Zheng and Stefanidis, and evidentiary reference Laidler.
Regarding instant claim 1, claim 1 of the reference application recites a method for producing a protein molded article comprising bringing a raw material containing a protein in which a hydroxyl group is esterified into contact with an acidic or basic medium, and claim 8 of the reference application recites that the esterified protein contains a formic acid ester.
The claims of the reference application do not recite the temperature of the basic medium comprising water, or that the formic acid ester is formed by the reaction of formic acid with a hydroxyl group in the esterified protein.
Yamashita relates to the treatment of cellulose esters generated by treatment with organic acids [abstract of the translation].
Regarding instant claims 1 and 5 and the limitation of bringing a raw material composition containing an esterified protein into contact with a basic medium, Yamashita discloses a method of preparing a cellulose ester by contacting cellulose with an organic acid [p 3, top paragraph], and treating the cellulose ester with an alkali (such as ammonia) wherein the liquid phase of the wet fibrillated cellulose ester is adjusted to pH of 5-9 [abstract] in order to suppress corrosion and acid odors resulting from ester hydrolysis [para 0004 of the translation]. Yamashita discloses that esters stored over a long period of time can become hydrolyzed and release free acid as a result, wherein the hydrogen ion of the free acid catalyzes more ester hydrolysis, and therefore adding alkali such as ammonia, NaOH and KOH would lower the hydrogen ion concentration and suppress the amount of free acid generated [p 5, section “Alkali Treatment Step”], therein limiting the free acid odors resulting from such hydrolysis in long-term storage [abstract]. Therefore Yamashita discloses a step of treating an esterified protein with a basic medium.
Stefanidis discusses general base catalysis of ester hydrolysis [title], and discloses that bases can bring about hydrolysis of esters by nucleophilic catalysis and by general base catalysis, wherein general base catalysis occurs by removing a proton from water for an attack on an acyl compound [p 6045, col 1, paras 1-2], and shows increasing rate of hydrolysis (kobs) with increasing base on formate esters in [Figure 1]. In view of Stefanidis, one of skill in the art would recognize that the treatment of an ester with a base as disclosed by Yamashita would still result in ester hydrolysis through general base catalysis, and also that said general base catalysis would not produce a free acid, thereby accomplishing the goal of Yamashita to prevent formation of free acid over time. Therefore the treatment of an esterified protein with an alkali as disclosed by Yamashita is considered to correspond to the step of contacting an esterified protein with a basic medium that results in ester hydrolysis.
Regarding instant claims 1 and 4 and the limitation of the basic medium between 40 °C to 180 °C (corresponding to instant claim 1) and between 40 °C and the boiling point (corresponding to instant claim 4), Yamashita discloses the cellulose ester solution is about 0 to 60 °C to facilitate the precipitation into a fibrous form [p 4, 4th paragraph]. While Yamashita does not explicitly disclose a basic medium between 40 °C to 180 °C (or the boiling point corresponding to claim 4), without any disclosure to suggest otherwise one of skill in the art would be reasonably expected to maintain the temperature of reactions throughout the method of Yamashita. Considering an alternative interpretation that Yamashita suggests altering temperature through the lack of an explicit disclosure of a temperature for ester hydrolysis, the disclosure of Stefanidis correspond to the hydrolysis of organic acid esters at 25 °C [p 6045, col 2, para 2], and according to MPEP 2144.05.II.A, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. As Stefanidis discloses the base hydrolysis of organic acid esters at 25 °C, one of skill in the art would have been motivated to increase the temperature to the claimed range in order to increase the rate of ester hydrolysis for a more efficient hydrolysis reaction, as reaction rate and temperature are understood to be directly related in chemical reactions as evidenced by Laidler [p 494, col 1, beginning at final paragraph].
Zheng discusses the O--formylation of proteins incubated in concentrated formic acid [title], and discusses that formic acid is among the most effective solvents for protein solubilization that can disrupt intramolecular hydrogen bonds to solvate polar amino acid residues, and has been employed to solubilize milk casein, wool keratin, collagen and silk proteins [p 1059, col 1, para 1].
Regarding instant claim 1 and the limitation of a protein containing a formic acid ester, Zheng discloses that the primary reaction product of formic acid with protein is O-formylation of Ser and Thr residues [p 1060, “Significance of the Study” section], which corresponds to the formation of a formic acid ester through the reaction of formic acid with a hydroxyl group in the protein [p 1060, col 1, para 1]. Zheng further discloses that this covalent modification of proteins is unfortunate as it can disrupt downstream applications such as Mass Spectrometry [p 1060, “Significance of the Study” section], therefore suggesting that formic acid addition bestows many benefits to protein solubilization that may require steps to address the O-formylation of proteins depending on the desired application.
While Yamashita discusses cellulose esters formed by the addition of an organic acid to cellulose, the ester bonds formed and their subsequent hydrolysis are considered to relevant to the O-formylated proteins of Zheng, as each of the esters of Zheng and Yamashita are understood to occur at the hydroxyl groups of the respective substrates (cellulose for Yamashita, and Ser/Thr residues of proteins such as collagen for Zheng), and as such, each esterified product would be expected to undergo base hydrolysis as disclosed by Stefanidis, as each esterified product contains an acyl group by definition.
In view of Zheng, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the reference application by using the O-formylated collagen ester of Zheng to arrive at the claimed invention, since the simple substitution of one known element for another results in a predictable result. One of ordinary skill in the art would have recognized that the O-formylated collagen of Zheng and the esterified protein of the reference application are both esterified proteins that contain a formic acid ester, and as such both are capable of being incorporated into such methods as described by the reference application. Thus it would have been obvious to one of ordinary skill in the art to replace the esterified protein of the reference application with the O-formylated collagen of Zheng, as one of ordinary skill in the art would have been able to carry out such a substitution with a reasonable expectation of success because both the reference application and Zheng discuss methods formic acid esters of proteins.
In view of Yamashita and Stefanidis, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the claims of the reference application by treating the ester with base at the claimed temperatures, as disclosed by Yamashita and Stefanidis, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the claims of the reference application by treating the ester with base at the claimed temperatures because Yamashita discloses treatment of an ester with a base at the claimed temperature to prevent the formation of free acid through storage, and both Yamashita and Stefanidis provide the general conditions of the incubation with base for hydrolysis through which one of skill in the art could arrive at the claimed range by routine optimization. One of ordinary skill in the art would have had a reasonable expectation of success because the reference application, Yamashita and Stefanidis all relate to the treatment of esters with base.
Regarding instant claim 3, Yamashita discloses the use of NaOH as the alkali, which is considered to correspond to an aqueous solution [p 5, section “Alkali Treatment Step”].
Regarding instant claim 6, claim 5 of the reference application recites that the protein is a structural protein.
Regarding instant claims 7 and 33, claim 6 of the reference application recites that the structural protein is fibroin.
Regarding instant claims 8 and 32, claim 7 of the reference application recites that the fibroin is spider silk fibroin.
Regarding instant claim 9, Zheng discusses the formation of formic acid esters as described above.
Regarding instant claims 10 and 31, claim 9 of the reference application recites that the raw material at least one selected from the group consisting of a fiber, a heat compression molded article, a film, a porous body, a gel, and a resin.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 11 is newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-9 of copending Application No. 17/764669 in view of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-10 and 31-33, and further in view of Brand.
The claims of the reference application and the disclosures of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-10 and 31-33 of this application are discussed above. The claims of the reference application do not recite a crimping step.
Brand discusses the mathematical principles of fiber crimp (title), including the contribution of fiber crimp to the final characteristics of the finished fabric [p 39, para 1].
Regarding instant claim 11, Brand discloses mathematical formulas relating the change in crimp of wool fibers and states "Q [is] the change in the spatial form of the crimp of a fiber when we change conditions such as temperature, humidity, etc." [p 41, col 1, para 2].
In view of Brand, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combined method of the reference application, Yamashita, Zheng and Stefanidis by adding the crimping step of Brand to alter the characteristics fiber and therefore the final fabric to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of the reference application, Yamashita, Zheng and Stefanidis by adding a crimping step, because Brand discloses that percentage of crimp in a fiber is related to its exposure to humidity, and therefore water in an aqueous solution, and the degree of crimp in a fiber contributes to the characteristics of the final fabric. One of ordinary skill in the art would have had a reasonable expectation of success because the reference application discusses industrial fiber formation processes, and Brand describes the mathematical relationships for determining physical characteristics of fibers.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 12 and 29 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-9 of copending Application No. 17/764669 in view of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-10 and 31-33, and further in view of Hormann and evidentiary reference Cavallaro.
The claims of the reference application and the disclosures of Yamashita, Zheng and Stefanidis as applied to instant claims 1, 3-10 and 31-33 are discussed above. The claims of the reference application do not recite a shrink-proofing step.
Hormann discusses reversible and irreversible denaturation of collagen fibers [title], and describes that native fibers shrink to about one-third of their original length when heated in water above 62 °C due to the denaturation of covalently cross-linked collagen molecules that transform the triple-helix structure to randomly coiled peptide chains [p 932, col 1, para 1], which can affect the mechanical properties of collagen as they are dependent on the degree of covalent crosslinking as evidenced by Cavallaro [p 785, col 2, para 2].
Regarding instant claim 12, Hormann discloses that denaturation (and therefore shrinkage) of collagen proceeds at a temperature below the shrinkage temperature given time, but only to a limiting value, as stabilizing lattice forces within the collagen fiber limit the progress to denaturation [p 937, col 1, para 2] as shown in by the treatment of collagen fibers of rattail tendons in water [Figure 4]. Hormann further discloses considerable renaturation and restoration of triple helix structure can be achieved at 20-30 °C following denaturation, wherein original lattice structure restoration is further promoted by stretching the fibers [p 937, col 1, paras 4-6]. Therefore one of skill in the art would be able to use the disclosure of Hormann to prevent shrinkage by contacting the fiber with water below the denaturation temperature of collagen, and could subsequently rescue the fiber from shrinkage by further cold storage of the fiber in water.
In view of Hormann, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of the reference application, Yamashita, Zheng and Stefanidis by adding a shrink-proofing proofing the fiber, as disclosed by Hormann, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of the reference application, Yamashita, Zheng and Stefanidis, because Hormann discloses methods to both reduce and reverse the shrinkage of collagen fibers by preventing denaturation and promoting renaturation that affects the mechanical properties of the fibers. One of ordinary skill in the art would have had a reasonable expectation of success because the reference application discusses industrial fiber formation processes, Zheng discusses the modification of collagen to enhance downstream applications, and Hormann describes strategies to maintain the structure of materials formed by collagen.
Regarding instant claim 29, Hormann does not disclose a protein fiber with a shrinkage rate of -5% to +5% as defined by Equation 1. Hormann however does disclose a method of reducing shrinkage of collagen and restoring shrinkage of collagen [p 937, col 1, para 2; p 937, col 1, paras 4-6]. According to MPEP 2144.05.II.A, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum workable ranges by routine experimentation. One of skill in the art would have been motivated apply the principles of Hormann to control protein fiber shrink rate, and would have had a reasonable expectation of success as Hormann discloses a range of temperatures and times to both prevent and restore shrinkage of collagen [Figures 4-6] before the effective filing date.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 13 is newly rejected provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-9 of copending Application No. 17/764669 in view of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-10 and 31-33 above, and further in view of Sutti.
The claims of the reference application and the disclosures of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-10 and 31-33 are discussed above. The claims of the reference application do not recite a hank state of fiber.
Sutti discusses fibers and fiber forming processes [title] that include production methods to overcome the common disadvantages in the field regarding difficulties purifying and isolating formed fibers [para 0004].
Regarding instant claim 13, Sutti discloses electrospinning to produce a continuous polymer fiber with controllable diameter, composition and fiber orientation (para 0002). While hank is not defined by the instant application, the term is known in the art as a unit of loose assemblage of fibers forming a single strand. Therefore the methods of Sutti satisfy the limitations of instant claim 13.
In view of Sutti, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined method of the reference application, Yamashita, Zheng and Stefanidis, to be applied to hank fiber as disclosed by Sutti to treat a fiber structure that has a controllable diameter, composition and fiber orientation. One of skill in the art would have been motivated to modify the combined method of the reference application, Yamashita, Zheng and Stefanidis, because Sutti discloses methods to overcome common disadvantages in the field purifying and isolating formed fibers. One of ordinary skill in the art would have had a reasonable expectation of success because both the reference application and Sutti discuss methods for industrial fiber-formation.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 14 is newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-9 of copending Application No. 17/764669 in view of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-10 and 31-33 above, and further in view of Lo
The claims of the reference application and the disclosures of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-10 and 31-33 are discussed above. The claims of the reference application do not recite a cloth state of fiber.
Lo discusses the uses of high molecular weight silk fibroin [title].
Regarding instant claim 14, According to MPEP 2144.04.IV.C, selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results. Lo discloses that silk fibroin from the silkworm Bombyx mori is a material that has been used as a cloth (p 0004), and that silk-based materials such as these have biomedical applications to produce high strength materials. As such, the silk fiber in cloth state still contains the same functional groups for the esterification and ester hydrolysis reactions as set forth in the prior art.
In view of Lo, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined method of the reference application, Yamashita, Zheng and Stefanidis, to be applied to cloth fiber in order to modify a fiber structure after processing into a cloth state for use in biomedical applications. One of ordinary skill in the art would have been motivated to modify the combined method of the reference application, Yamashita, Zheng and Stefanidis, because Lo discloses that silk fibers can be used as cloth for biomedical applications, and the fiber in cloth state still bears the same functional groups for the esterification and ester hydrolysis reactions. One of ordinary skill in the art would have had a reasonable expectation of success because the reference application discusses industrial fiber formation processes, and Lo describes different fibers and their downstream applications as cloth materials.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 15 and 28 are newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-9 of copending Application No. 17/764669 in view of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-10 and 31-33 above, and further in view of Hu.
The claims of the reference application and the disclosures of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-10 and 31-33 are discussed above, of which some disclosures similarly apply to claim 15 discussed herein. In summary, regarding the limitations of instant claims 15 and 28, claim 1 of the reference application discloses a method wherein a protein is esterified and brought into contact with an acidic or basic medium. The claims of the reference application do not recite the use of water vapor.
Hu discusses methods to obtain refined control of the molecular structure of silk biomaterials through temperature-controlled water vapor annealing or TCWVA [abstract].
Regarding the limitations recited in claims 15 and 28 of using water vapor for the hydrolysis reaction, Hu discloses "a method… to regulate the interaction of proteins and water molecules … can promote protein crystallization during interaction with water molecules but avoid possible dissolution" [p 1687. col 1, para 1], wherein TCWVA is described as "a new physical approach to control the structure of fibrous protein" [p 1687, col 1, para 2] using silk fibroin [p 1687, col 1, para 3] at a variety of temperatures ranging 4 - 100 °C [Table 1].
In view of Hu, it would have been obvious to one of ordinary skill in the art before the effective filing date to modify the combined method of the reference application, Yamashita, Zheng and Stefanidis, by using water vapor for the hydrolysis reaction in order to regulate the interaction of protein and water molecule and allow for control of fibrous protein structure. One of ordinary skill in the art would have been motivated to modify the combined method of the reference application, Yamashita, Zheng and Stefanidis, because Hu discloses that using the temperature-controlled water vapor annealing method regulates the interaction of protein and water molecules that allows the control of fibrous protein structure. One of ordinary skill in the art would have had a reasonable expectation of success because the reference application discusses industrial fiber formation processes using modified protein substrates, and Hu describes a method to control the structure of fiber proteins during modification reactions.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 34 is newly provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5-9 of copending Application No. 17/764669 in view of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-10 and 31-33 above, and further in view of Guinea.
The claims of the reference application and disclosures of Yamashita, Zheng and Stefanidis as applied to claims 1, 3-10, 31-33. The claims of the reference application do not recite the shrinkage rate of spider silk fibroin fibers.
Guinea relates to the stretching of supercontracted fibers [title], and discusses methods of measuring the effect on tensile strength of stretching silk fibers in an aqueous environment [abstract].
Regarding instant claim 34, Guinea discloses spider silk fibers are known to undergo supercontraction if unrestrained in water resulting in 50% shrinkage of its initial length and a dramatic change in mechanical behavior [p 25, col 2, para 2], and describes a method of applying force to the spider silk fibers to achieve a desired length in [Figure 2], wherein fiber length is shown to be doubled from the supercontracted state upon stretching corresponding to approximately the original length of the fiber before supercontraction, which is considered to correspond to the shrinkage rate limitations of the claim. Guinea further discloses the stretching corresponds to better alignment of the protein chains resulting in increased stiffness [p 28, col 1, para 2], that the stretching and drying process enables production of spider silk fibers with a tailored and pre-established stress-strain profile in a reliable and repetitive way, and offers the possibility of reproducing the full range of tensile properties exhibited by spider silk fibers [p 28, col 2, beginning at para 3].
In view of Guinea, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combined method of the reference application, Yamashita, Zheng and Stefanidis by adding a step to stretch the spider silk fiber, as disclosed by Guinea, to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to modify the combined method of the reference application, Yamashita, Zheng and Stefanidis, because Guinea discloses the stretching and drying process enables production of spider silk fibers with a tailored and pre-established stress-strain profile in a reliable and repetitive way, and offers the possibility of reproducing the full range of tensile properties exhibited by spider silk fibers. One of ordinary skill in the art would have had a reasonable expectation of success because the refence application discusses industrial fiber formation processes using spider silk fibroin, and Guinea discusses methods of modulating spider silk fiber shrinkage to tune the stress-strain profile of spider silk fibers.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Remarks: beginning on page 9 of Applicants response to double patenting rejections; Applicant in summary contends the double patenting rejections should be withdrawn as according to MPEP 804.I.B.1(b)(i) the current application under examination has an earlier patent term filing date, and if a provisional non-statutory double patenting rejection is remaining in such an application, the examiner should withdraw the provisional rejections upon issuance of the patent.
Applicant’s remarks are considered and found not convincing. The provisional NSDP rejections in the previous Office action were withdrawn above in view of the instant amendments to the claims, however the current provisional NSDP rejections of record set forth above will not be withdrawn as the instant application has not issued as a patent.
Conclusion
Claims 1, 3-15, 28-29 and 31-34 are pending.
Claims 1, 3-15, 28-29 and 31-34 are rejected.
No claim is in condition for allowance.
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/JOSEPH R SPANGLER/
Examiner
Art Unit 1656
/David Steadman/Primary Examiner, Art Unit 1656