DETAILED ACTION
This application is a continuation of U.S. Patent Application No. 16/538,519 filed August 12, 2019, which claims the benefit of U.S. Provisional Application No. 62/717,622, filed August 10, 2018, the entire contents of which are incorporated by herein by reference for all purposes.
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 .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/29/2024 has been considered by the examiner.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 38-40, 42, 43, 48-51, 54, 56-59, 61, 62 and 72-76 are rejected under 35 U.S.C. 103 as being unpatentable over Islam et al. (US 2004/0102614). Additional supporting evidence provided herewith by Gosline et al. (US 7,049,405) (All of record).
With respect to claim 38, Islam teaches a process for preparing a molded body (“methods for spinning biofilament fibers from recombinant spider silk proteins”, Pa [0006]), comprising the steps of:
(a) providing a first composition (“the dope solution”) comprising a recombinant spider silk protein admixed with a plasticizer, wherein the first composition is capable of being induced into a flowable state (“a solution of recombinant spider silk protein. The solvent used for the dope solution of the present invention can be any aqueous solution in which the spider silk protein is soluble… useful buffers include… ascorbate”, Pa [0093]; “ascorbate” is an exemplary plasticizer in the instant specification (“ascorbic acid”, Pa [0132]));
(b) applying pressure and shear force to the first composition to induce the flowable state and form a first melt composition in the flowable state (“The extrusion unit enables control of the dope flow rate”, Pa [0102]; “facilitate the application of shear stress”, Pa [0103]; Islam’s extrusion inherently accompanies applying pressure and shear force, and inherently makes the dope solution flowable through the spinneret.), and
(c) extruding the first melt composition to form an extrudate, wherein the extrudate is a first molded body (“spinning”, Pa [0103]), wherein the process is free of a coagulation bath (“The process forms a continuous filament of semi-solid polymer, and the resulting filament is then solidified, usually by drying (dry spinning)”, Pa [0043]); “the dope to dry spinning, i.e., extrusion directly into air and to the steps of drawing and spinning, without immersion in a coagulation bath or wash.”, Pa [0096]).
In this embodiment, Islam does not explicitly teach that the first composition comprises a recombinant spider silk protein powder admixed with a plasticizer and a beta-sheet content present the first molded body is substantially the same as a beta-sheet content present in the recombinant spider silk protein powder.
In another embodiment (Examples 1-2), Islam further teaches that MaSpII protein in the form of a pellet was recovered from transgenic goat milk (Pa [0156]), the pellet was carefully ground with a glass rod to obtain a homogeneous mixture with guanidine-HCl, by buffer exchange chromatography, Guanidine-HCl was removed and the MaSpII solution (MaSpII spider silk protein in 50 mM glycine buffer at pH 11) is prepared (Pa [0156]-[0160]). That is, Islam teaches the dope solution prepared with MaSpII protein in the form of a ground pellet, i.e., a powder, and the buffer. Furthermore, Islam previously teaches that the solvent used for the dope solution of the present invention can be any aqueous solution in which the spider silk protein is soluble, and a preferred buffer solution for use in the dope solutions of the present invention is 50 mM glycine, and other useful buffers include ascorbate which is recited in the instant specification (Pa [0132]) as an example of the plasticizers.
Since Islam teaches substitutability of ascorbate for glycine, one would have found it obvious to prepare the dope solution with MaSpII spider silk protein powder and ascorbate (the plasticizer) for the purpose of further biofilament spinning.
With respect to claim 39, Islam as applied to claim 38 above further teaches that extruding the first melt composition comprises extruding the first melt composition to form a fiber (“the fiber spinning process”, Pa [0096]).
With respect to claim 40, Islam as applied to claim 39 above further teaches that extruding the first melt composition to form the fiber comprises extruding the first melt composition through a spinneret (“the extrusion unit houses the spinneret through which the dope is passed.”, Pa [0102]).
With respect to claim 42, Islam as applied to claim 38 above further teaches that the process further comprises (d) applying pressure and shear force to the first molded body to transform the first molded body to a second melt composition which is in a flowable state, and (e) extruding the second melt composition in the flowable state to form a second molded body (“Spider silks can be made into film by further attenuation of the spinning process. The extruded filament can be processed through a pair of rotating coated pressing roller nips or inflated apron nips. Adjusting the flow rates and pressure on the nip rollers or inflated apron nip can control the thickness, width, and fineness of the film.”, Pa [0149]).
With respect to claim 43, even though Islam as applied to claim 42 above is silent to repeating steps (c) and (d) to the second molded body at least once, one would have found it obvious to merely repeat processing the film through a pair of rotating coated pressing roller nips or inflated apron nips in order to obtain the desired film without any new or unexpected results.
With respect to claim 48, Islam as applied to claim 38 above further teaches that an instrument (“extrusion unit”, Pa [0102]) used to apply the shear force and pressure comprises a mixing chamber (the upper part of the extrusion unit) that is coupled to and proximal to an extrusion chamber (the lower part of the extrusion unit including the spinnerets).
With respect to claim 49, Islam as applied to claim 48 above further teaches that the first composition is heated in the mixing chamber or in the extrusion chamber (“The extrusion unit …can be regulated by a heating … jacket.”, Pa [0102]; “The spinneret is maintained and is held at temperatures below 100° C”, Pa [0104]).
With respect to claim 51, Islam as applied to claim 49 above further teaches that the first composition is heated to a temperature of less than 120° C (“The extrusion unit …can be regulated by a heating … jacket.”, Pa [0102]; “The spinneret is maintained and is held at temperatures below 100° C”, Pa [0104]).
With respect to claim 54, Islam as applied to claim 38 above further teaches that the first molded body after extrusion has a loss of water content of less than 15% as compared to the first composition before extrusion (“the biofilament must be dried.”, Pa [0115]; “Water retention of spun fibers preferably is close to that of natural silk fibers, i.e., 11%.”, Pa [0128]).
With respect to claim 56, Islam as applied to claim 48 above does not explicitly teach that the first composition has a residence time in the mixing chamber ranging from 3 to 7 minutes. However, Islam further teaches that the dope solution is extruded at a linear speed as low as about 0.1, 0.2, 0.4, or 0.6 m/min, or as rapidly as about 4.0, 6.0, 8.0, or 10.0 m/min (Pa [0012]), and the residence time would vary depending on which portion of the mixing chamber the dope solution is placed as well as the extruding speed. Thus, one would have found it obvious to select the optimum residence time of the composition in the mixing chamber by routine experimentation for the purpose of extruding the desired fiber.
With respect to claim 57, Islam as applied to claim 48 above further teaches that the extrusion chamber is tapered proximal to an orifice through which the first melt composition is extruded (“In spinnerets with multiple orifices, a converging constant taper, resulting in a conical or funnel shape, has been shown to facilitate the application of shear stress during spinning”, Pa [0103]).
With respect to claim 58, Islam as applied to claim 48 above further teaches that the extrusion chamber is temperature controlled (“The extrusion unit …can be regulated by a heating … jacket.”, Pa [0102]).
With respect to claim 59, Islam as applied to claim 48 above further teaches that the first molded body is a fiber and the fiber is drawn over multiple steps (“Drawing is preferably done using a set of godets, with the filament wrapped several times (e.g. 3-8 times) around the chromium roller of each godet.”, Pa [0112]).
With respect to claims 61 and 62, Islam as applied to claim 48 above does not explicitly teach that the recombinant spider silk protein is substantially non-degraded in the first molded body. However, Islam further teaches that numerous useful polymers thermally degrade when heated in melt spinning (Pa [0045]). That is, Islam discloses the problem of degradation by heating in melt spinning. Islam further teaches that the spinneret is maintained and is held at temperatures below 100° C (Pa [0104]). Thus, one would have found it obvious to adjust the temperature during the dry spinning for the purpose of obtaining the fiber having non-degraded recombinant spider silk protein.
With respect to claim 72, Islam as applied to claim 38 above further teaches that the plasticizer is water (Pa [0144]).
With respect to claim 73, Islam as applied to claim 38 above further teaches that the first molded body is a fiber (“The spun fibers”, Pa [0018]).
With respect to claim 74, Islam as applied to claim 73 above further teaches that the fiber has a strength in the range of 100 Pa to 1.2 GPa (“The tensile strength of biofilaments spun by the methods of the present invention generally range from 0.03 g/d to 10 g/d”, Pa [0018] which provides 0.027 to 9 MPa.).
With respect to claim 75, Islam as applied to claim 38 above further teaches that the solvent used for the dope solution is an aqueous buffer solution with a pH from about 4 to about 12, and useful buffers include ascorbate (Pa [0093]) which is an exemplary plasticizer in the instant specification (“ascorbic acid”, Pa [0132]). Thus, Islam teaches the dope solution consisting of recombinant spider silk protein and ascorbate, and it meets the claim.
With respect to claim 76, Islam as applied to claim 38 above further teaches that preferably the biofilament protein, when subjected to shear forces and mechanical extension, has a polyalanine segment that undergoes a helix to a β-sheet transition, where the transition forms a β-sheet that stabilizes the structure of the protein (Pa [0078]), and Gosline as the additional supporting evidence also teaches that upon stretching, α-helices in the protein filaments are converted to β-sheet forms, which may include β-sheet crystals (co 1 li 61-63), the α-helical structures contained within the α-helical protein based materials of this invention can be converted from their native state to a β-sheet conformation, this process usually involves crystallization of protein chains in the extended chain conformation and provides improved strength, stiffness and/or toughness while reducing extensibility, the conversion is achieved by drawing the fibre or film in the dry or wet state (co 9 li 5-12). Since Islam’s first molded body (the extruded fiber) has not been stretched or drawn, one would appreciate that any substantial conversion to a β-sheet conformation has not been occurred. Therefore, one would appreciate that a beta-sheet content present the first molded body is substantially the same as a beta-sheet content present in the recombinant spider silk protein powder.
Claims 44, 46, 47, 68 and 69 are rejected under 35 U.S.C. 103 as being unpatentable over Islam et al. (US 2004/0102614) as applied to claim 38 above, and further in view of Orcutt et al. (US 2008/0254199) (All of record).
With respect to claims 44, 46 and 68, Islam as applied to claim 38 above does not explicitly teach that said shear force is from 1.5 to 13 Nm.
In the same field of endeavor, extruding a protein product with protein fibers, Orcutt teaches that the pre-mix is subjected to shear and pressure by the twin-screw extruder to plasticize the mixture, the screw speed determines the amount of shear and pressure applied to the mixture, and moves the mixture through the extruder at a rate of at least about 20 kilograms per minute which is at least 3.3 Nm/sec (Pa [0083] and [0085]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Islam with the teachings of Orcutt such that the one would substitute Orcutt’s twin-screw extruder for Islam’s extruder in order to form fibers, since it has been held that the use of a known technique to improve similar devices (methods or products) in the same way is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, C.).
With respect to claim 47, Orcutt as applied in the combination regarding claim 46 above further teaches that the screw speed of the twin screw extruder ranges from 200 to 500 RPM during application of said pressure and shear force (Pa [0085]). In the case where claimed ranges “overlap or lie inside ranges disclosed by prior art” a prima facie case of obviousness exists. (See MPEP 2144.05 (I)).
With respect to claim 69, Islam as applied to claim 38 above does not explicitly teach that the first composition is induced into the flowable state through the application of pressure ranging from 1 MPa to 300 MPa.
In the same field of endeavor, extruding a protein product with protein fibers, Orcutt teaches that the pre-mix is subjected to shear and pressure by the twin-screw extruder to plasticize the mixture, the screw speed determines the amount of shear and pressure applied to the mixture, and the extruder generates an extruder head pressure of from about 500 to about 3000 psig which is 3.45 to 20.7 MPa (Pa [0083] and [0085]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Islam with the teachings of Orcutt such that the one would substitute Orcutt’s twin-screw extruder for Islam’s extruder in order to form fibers, since it has been held that the use of a known technique to improve similar devices (methods or products) in the same way is likely to be obvious. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, C.).
Claim 65 is rejected under 35 U.S.C. 103 as being unpatentable over Islam et al. (US 2004/0102614) as applied to claim 62 above, and further in view of Joerg et al. (US 2017/0368174) (All of record).
With respect to claim 65, Islam as applied to claim 62 above does not explicitly teach that the degradation of the recombinant spider silk protein is assessed by measuring the amount of full-length recombinant spider silk protein present in the first composition before and after extrusion using size exclusion chromatography.
Joerg relates to pharmaceutical products comprising stable liquid pharmaceutical compositions including proteins (Pa [0002] and [0038]). Joerg further teaches that chemical stability can be assessed by detecting and quantifying chemically altered forms of the protein by degradation processes including hydrolysis or clipping (evaluated by methods such as size exclusion chromatography [SEC]) (Pa [0040]).
One would have found it obvious to measure the length of the recombinant spider silk proteins by size exclusion chromatography in order to assess the amount of degradation.
Claim 67 is rejected under 35 U.S.C. 103 as being unpatentable over Islam et al. (US 2004/0102614) as applied to claim 38 above, and further in view of Shoseyov et al. (US 2018/0193524) (All of record).
With respect to claim 67, Islam as applied to claim 38 above further teaches that the extrusion through the spinneret applies shear stress during spinning to achieve molecular alignment (Pa [0103]), the drawing process improves the axial orientation and toughness of the biofilament develop end-use properties such as modulus and tenacity (Pa [0111]), and the filaments show good birefringence properties (Pa [0139]). Islam further teaches that for the best lot in this experiment, drawing twice in the bath to a final draw ratio of approximately 4, resulted in the good mechanical properties (Pa [0163]), but does not explicitly teach the birefringence of 5 X 10-5 to 0.04 as measured by polarized light microscopy.
In the same field of endeavor, method of generating collagen fibers, Shoseyov teaches that draw ratio, birefringence, and mechanical properties of drawn gibers are related (Pa [0308]-[0321]), and birefringence of the spun fiber is measured by polarized microscopy (Pa [0309]). In Figs. 5A-5D, between DR 1:3.3 and DR 11.4 the fibers show good in most mechanical properties, and in that DR range the birefringence is about 0.003 to 0.03 (Fig. 10).
One would have found it obvious to perform drawing the fibers to obtain the drawn fibers having the birefringence within the range taught by Shoseyov for the purpose of obtaining the fibers having good mechanical properties.
Claim 70 is rejected under 35 U.S.C. 103 as being unpatentable over Islam et al. (US 2004/0102614) as applied to claim 38 above, and further in view of Li et al. (US 2013/0253121) (All of record).
With respect to claim 70, Islam as applied to claim 38 above does not explicitly teach that the first composition has a melt flow index of at least 0.5, at least 1, at least 2, or at least 5 as tested per ASTM D1238 at 95° C. with a load of 2.16 kg.
Li relates to a pellet being used directly extrusion molding, fiber and tap applications (Pa [0020]), and Li teaches that each exemplary polymer in each embodiment has a melt flow rate (or melt index) being from 0.5 g/10 min. to 50 g/10 min as determined in accordance with ASTM D1238 condition “L” (Pa [0024]), from 0.5 g/10 min. to 500 g/10 min as determined in accordance with ASTM D1238 (Pa [0027]), from 0.5 g/10 min. to 500 g/10 min as determined in accordance with ASTM D1238 (Pa [0034] and [0036]), etc. (Pa [0047], [0048], [0061], [0065]).
Since Islam teaches adjusting a viscosity by adding additives (Pa [0096]), one would have found it obvious to adjust the melt flow index of the composition in a range taught by Li for the purpose of forming a fiber. Even if Li does not explicitly teach that the claimed range of the melt flow index, in the case where claimed ranges “overlap or lie inside ranges disclosed by prior art” a prima facie case of obviousness exists. (See MPEP 2144.05 (I)).
Claim 71 is rejected under 35 U.S.C. 103 as being unpatentable over Islam et al. (US 2004/0102614) as applied to claim 38 above, and further in view of Kittleson et al. (US 2018/0282381) (All of record).
With respect to claim 71, Islam as applied to claim 38 above further teaches that the recombinant spider silk protein comprises at least two occurrences of a repeat unit (“Sequencing of spider silk proteins has revealed that these proteins are dominated by iterations of four simple amino acid motifs”, Pa [0051]), but does not specifically teach that the repeat unit comprises more than 150 amino acid residues and having a molecular weight of at least 10 kDa; an alanine rich region with 6 or more consecutive amino acids, comprising an alanine content of at least 80%; and a glycine rich region with 12 or more consecutive amino acids, comprising a glycine content of at least 40% and an alanine content of less than 30%.
In the same field of endeavor, methods for producing high secreted yields of recombinant proteins, Kittleson teaches that silk proteins are large proteins (>150 kDa, >1000 amino acids), in which a repeat domain (REP) blocks of amino acid sequences (“repeat units”) that are at least 12 amino acids long and that are repeated and that can comprise 2 to 10 amino acid long sequence motifs, REPs typically make up about 90% of the native spider silk proteins, and assemble into the alanine-rich nano-crystalline (<10 nm) domains (likely made up of alternating beta sheets) and glycine-rich amorphous domains (possibly containing alpha-helices and/or beta-turns) (Pa [0065]). Kittleson further teaches that the silk or silk or silk-like proteins comprise more than 6 exact-repeat and/or quasi-repeat units that are alanine-rich, consecutive amino acids that are more than 80% alanine (Pa [0069]), and the silk or silk or silk-like proteins comprise one or more glycine-rich exact-repeat and/or quasi-repeat units that are from 20 to 100 amino acids long and comprise 25-50% glycine and 10-40% alanine (Pa [0070]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify Islam with the teachings of Kittleson such that the one would substitute Kittleson’s silk protein for Islam’s recombinant spider silk protein for the purpose of producing high secreted yields of recombinant proteins.
Conclusion
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/YUNJU KIM/Primary Examiner, Art Unit 1742