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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/6/2026 has been entered.
DETAILED ACTION
Claims 2-4, 15, 17-22, and 25 are cancelled. Claims 1, 5-14, 16, and 23-24 are pending and under examination on their merits.
The nonstatutory double patenting rejection over 17/972,186 is withdrawn in light of the terminal disclaimer filed on 01/06/2026.
Response to Arguments
Applicant's arguments filed 1/6/2026 have been fully considered but they are not persuasive.
Applicant argues against the written description rejection of claims under 35 U.S.C. 112(a) on the grounds that a skilled artisan would appreciate that lyophilization results in highly porous MaSp powder regardless of the liquid/fiber weight ratio (Arguments, paragraph 4 on page 6).
In response, this argument is unpersuasive because “highly porous” is not necessarily a BET surface area of between 100 m2/g and 5000 m2/g. Furthermore, claim 1 recites “a composition” rather than a lyophilized or dried composition. Applicant exemplifies a lyophilized composition of MaSp characterized by a BET surface area of 180 m2/g (Example 5 of the specification), whereas the claim recites a composition comprising MaSp characterized by a BET surface area of between 100 m2/g and 5000m2/g. The claimed BET surface area is an order of magnitude greater than the BET surface area for high surface area materials such as pure activated carbon (697 m2/g, see Table 1 of Roberts et al. Molecules 25.5 (2020): 1207). Roberts teaches that regenerated silk fiber has a BET surface area less than 100 m2/g (Table 1). Thus, neither the specification nor the prior art disclose any species of porous MaSp characterized by a BET surface area approaching the upper limit of the claimed range (5000 m2/g). Therefore, Applicant has not demonstrated possession of the claimed invention.
Declaration under 37 CFR 1.132
The declaration under 37 CFR 1.132 filed 1/6/2026 is insufficient to overcome the rejection of claims 1, 5-14, 16, and 23-24 based upon lack of written description under 35 U.S.C. 112(a) as set forth in the last Office action because: the evidence is not commensurate in scope with the claimed invention. The declaration sets forth experimental data that demonstrates that the lyophilization process does not compromise MaSp morphology and that the lyophilized MaSp retains its characteristic fluffy and voluminous structure regardless of MaSp concentration and solvent volume (Declaration, page 3, paragraph 3).
The claims recite a porous major ampullate spidroin protein characterized by a BET surface area of between 100 m2/g and 5000 m2/g. However, the specification only exemplifies a MaSp with a surface area of 180 m2/g (Example 5, [0305] of the specification). The specification and the prior art do not teach a structure-function relationship between the MaSp and the BET surface area. Although the specification sets forth that lyophilization with the solvent t-butanol increases the BET surface area of the MaSp, no examples are provided in which lyophilization increases the MaSp surface area to 5000 m2/g. The declaration fails to provide evidence that the inventors were in possession of the claimed genus because BET surface area is not provided in the experimental data (see Table 1 of the Declaration). No data is provided in which the MaSp particles have a BET surface area approaching 5000 m2/g.
Claim Objections
Claims 1, 13, and 16 are objected to because of the following informalities: there is a space missing between 100 and ppm. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 5-14, 16, and 23-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 is drawn to a composition comprising a porous major ampullate spidroin protein (MaSp), wherein the MaSp is characterized by a BET surface area of between 100 m2/g and 5000 m2/g and a residual amount of tert-butanol below 100 ppm, wherein the MaSp is in the form of particles having an average size in the range between 0.5 microns and 2 microns. The broadest reasonable interpretation of claim 1 includes liquid compositions as well as dried or lyophilized composition because the claim preamble does not limit the state of the composition of matter.
Claim 13 is drawn to a method for obtaining a dried major ampullate spidroin protein (MaSp), comprising mixing a MaSp with a liquid containing an organic solvent to obtain a mixture, and removing the liquid from the mixture by lyophilization, thereby obtaining a dried MaSp characterized by a BET surface area of between 100 m2/g and 5000 m2/g and a residual amount of t-butanol below 100 ppm. The composition of the liquid is not limited to aqueous solutions with t-butnaol as the only organic solvent (“containing” is interpreted as open).
The specification discloses the recombinant production of major ampullate spidroin (MaSp)-based fiber using bacteria ([0291]). The obtained pellet of fiber was washed with t-butanol and then t-butanol was added to the fiber to create a homogeneous suspension ([0292]). After centrifugation, the fiber was dried by lyophilization (freezing the fiber with liquid nitrogen and then applying a vacuum, see [0292]). The specification discloses that vacuum is applied to the frozen suspension until complete evaporation of the solvent occurs ([0292]). Figures 1A, 1C and 1E present the results of fibers obtained after purification and lyophilization with t-butanol, compared to analogous fibers lyophilized from water ([0293]). The specification further discloses that surface areas were determined from nitrogen adsorption data using the BET (Brunauer, Emmett, Teller) method ([0303]). The calculated surface area of SVX (spider silk protein expressed in bacteria) dried from t-butanol was about 180 m2/g, whereas the calculated surface area of SVX dried from water was about 85 m2/g ([0305]). Figures 1A, 1C, and 1E demonstrate via SEM images that the fiber is in the form of particles with a diameter ranging from 0.5 to 2 microns (see also [0031]).
In sum, the specification discloses a single species of the claimed genus of MaSp-based fiber in the form of particles with a characteristic size ranging from 0.5 to 2 microns that are characterized by a BET surface area of 180 m2/g and a residual amount of t-butanol. The specification also does not disclose the structure-function relationship between the BET surface area of the MaSp and the method conditions.
Arcidiacono et al. (Macromolecules 2002, 35, 1262-1266; cited in the Non-Final Action mailed on 5/13/2025) teaches aqueous processing and fiber spinning of recombinant spider silks: fibers were first spun into a coagulation bath containing methanol and water, after which the fibers were removed from the bath for evaluation (page 1263, left column, Fiber Spinning). However, Arcidiacono does not teach the BET surface area of the resulting fibers.
Roberts et al. (Molecules 25.5 (2020): 1207) teaches porous silk/activated-carbon composite fibers for adsorption and repellence of volatile organic compounds (Title). Roberts teaches reprocessing silkworm silk into aqueous regenerated silk fibroin (RSF) solutions before spinning into porous fibers via two cryogenic spinning techniques: Cryogenic Solution Blow Spinning (Cryo-SBS) and Cryogenic Wet Spinning (Cryo-WS) (paragraph 2 on page 2). By spinning colloidal suspensions of activated carbon (AC) in RSF, macroporous fibres loaded with AC can be obtained—increasing the specific surface area (SSA) (paragraph 2 on page 2). For the Cryo-WS method, RSF and colloidal RSF-activated carbon (AC) mixtures were wet-spun into an ethanol coagulation bath (page 3, 2. Results, paragraph 1, Figure 1(b)). The wet fibers were then subjected to solvent exchange in deionized (DI) water, before being rapidly frozen by submersion in liquid nitrogen followed by freeze-drying (page 3, 2. Results, paragraph 1). Roberts teaches in Table 1 the various BET surface areas for regenerated silk fibroin loaded with different wt% of activated carbon. The BET surface area of pure activated carbon is 697 m2/g, whereas 25% loading of the fiber results in 210 m2/g. Fiber without activated carbon (0 wt% AC) has a BET surface area less than 100 m2/g (Table 1). Roberts suggests the use of genetically engineered silks, such as recombinant spider silk, to tune the mechanical and textural properties of the silk or to introduce chemical functionality such as additional lysine groups to neutralize toxic VOCs or other substances (page 5, 3. Conclusions). However, Roberts produces thread-like porous particles that have a diameter 25-60 microns (Figure 1(d) and page 3, 2. Results, paragraph 1), which is distinct from the size of the presently claimed particles.
The prior art of Teagarden et al. (European Journal of Pharmaceutical Sciences 15.2 (2002): 115-133) teaches that tert-butanol/water is used as a co-solvent system in the freeze-drying of pharmaceutical products (Abstract). Teagarden teaches that one pharmaceutical product is manufactured by freeze-drying from a 20% v/v tert-butanol/water co-solvent system (page 115, right column, top paragraph). Teagarden teaches numerous reasons why freeze-drying with an organic solvent system can be desirable: the process increases rate of sublimation and decreases drying time, increases chemical stability of the pre-dried bulk solution, increases chemical stability of the dried product, increases drug wettability and solubility in solution, decreases reconstitution time, and enhances sterility assurance for pre-dried bulk solution (page 1515, right column, bottom paragraph). However, Teagarden also teaches that other co-solvent systems which do not freeze completely in commercial freeze-dryers were more difficult to use and often resulted in unacceptable freeze-dried cakes (Abstract). Teagarden teaches a variety of organic solvents evaluated in freeze-drying (Table 1) as well as systems with drug preparations freeze-dried from co-solvents (Table 2). The person of ordinary skill in the art would have been unable to predict based on the state of the art the effect of different mixtures of organic solvents comprising t-butanol on the BET surface area of a MaSp-based fiber.
Lyophilizing porous MaSp particles from a tert-butyl alcohol mixture (resulting in a residual amount of tert-butyl alcohol below 100 ppm) would have had an unpredictable effect on the surface area of the particles based on the state of the art.
Lu et al. (Cellulose 25.1 (2018): 619-629) teaches that freeze-drying fibrillated cellulose fiber from a water and TBA mixture results in the construction of a spider web-like structure because: (1) TBA molecules promote the separation of microfibrils and (2) the presence of TBA changes the morphologies and growth kinetics of ice-crystals (Abstract, right column). However, Lu’s fibrillated cellulose is a polysaccharide-based structure and does not comprise protein-based particles.
Teagarden et al. (European Journal of Pharmaceutical Sciences 15.2 (2002): 115-133; cited in the Non-Final Action mailed on 5/13/2025) teaches that TBA causes ice to form needle-shaped crystals and that as these needle-shaped crystals sublime, they create a more porous, less resistant matrix, which facilitates drying (bottom of left column on page 119 to top of right column on page 119). Teagarden also teaches that tert-butanol sublimes during primary drying and creates a porous structure, which facilitates the mass transfer of water vapor (left column on page 121). Teagarden teaches freeze-drying from a cosolvent such as TBA can improve drug product stability (page 123, left column, 5. Stabilization of freeze-dried product). However, Teagarden cautions that there are cases where the lyophilization of a protein from co-solvents can produce a less stable system (page 123, right column, second paragraph).
In sum, the person of ordinary skill in the art would have been unable to predict based on the state of the art the effect of tert-butyl alcohol or liquids containing mixtures of organic solvents with tert-butyl alcohol on the surface area of porous MaSp particles prepared by freeze-drying.
Based on the above analysis, the person of ordinary skill in the art would not have recognized that the inventors were in possession of the claimed genus of MaSp particles comprising between 100 m2/g and 5000 m2/g BET surface area and a residual amount of t-butanol less than 100 ppm. The person of ordinary skill in the art would not have recognized that the inventors were in possession of the claimed genus of drying methods capable of producing MaSp particles comprising between 100 m2/g and 5000 m2/g BET surface area and a residual amount of t-butanol less than 100 ppm.
Conclusion
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/CANDICE LEE SWIFT/Examiner, Art Unit 1657