DETAILED ACTION
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 .
Summary
Claims 1-29 are pending in this office action. All pending claims are under examination in this application.
Priority
The current application was filed on September 8, 2023 is a 371 of PCT/US2022/024632 filed on April 13, 2022, which in turn claims domestic priority to provisional patent application 63/177,613 filed April 21, 2021.
Information Disclosure Statement
Receipt of the Information Disclosure Statement filed on September 8, 2023 is acknowledged. A signed copy of the document is attached to this office action.
Duplicate Claim Warning
Although the claims are not identical, the groups designated within claims 14 and 16 are inclusive of one another. In a similar fashion, claims 19 and 21 are related.
Applicant is advised that should claims 14 and 19 be found allowable, claims 16 and 21 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01 (m).
Claim Objections
Claims 7, 9, and 27 are objected to because of the following informalities:
Claim 7 appears within the earlier claim set. However, claim 7 was unintendedly deleted, and the text of the claim was placed within claim 8. This error was reflected within the overall claim count of 28 in the earlier claim set, and 29 in the amended claim set.
Claim 9 has the text “Iridium” capitalized. The text should all be lowercase.
Claim 27 needs additional text to be amended after “claim 1” to have the claim make sense.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or non-obviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-29 are rejected under 35 U.S.C. 103 as being unpatentable over Serrano-Garcia et al. (US2018/0226582A1) in view of Yu (CN103572408A), DeMattei et al. (US2009/0012033A1), Park et al. (US2011/0204297A1), Reches et al. (WO2006/027780A2), and Mohanty et al. (WO2020/086812A1).
[The Examiner is going to introduce each new reference and then combine them where appropriate to reject the instant claims.]
1. Serrano-Garcia et al.
Serrano-Garcia et al. is considered the closest prior art as it teaches coaxial semiconductive organic nanofibers and electrospinning fabrication thereof (see title). In addition, Serrano-Garcia et al. disclose a coaxial nanocomposite including a core, which includes fibers of a first organic polymer, and a shell, which includes fibers of a second organic polymer, the first polymer and the second polymer forming a heterojunction (see abstract).
2. Yu
Yu teaches core-shell structure electroactive composite fibers and preparation method of tissue engineering scaffold (see title). Furthermore, Yu discloses that the invention has a preparation method of an electroactive micron/nanometer fiber scaffold which takes a degradable polymer as a shell and a conductive polymer as a core, has a core-shell structure and is formed by interlacing of composite fibers. The preparation method comprises the steps of preparing core spraying liquid; preparing shell spinning liquid; preparing conductive high-polymer/degradable polymer composite fibers with an electroactive core-shell structure and a composite fiber dual-pore structure scaffold by using a coaxial co-spinning device and combining a spinning technology with a spraying technology; cleaning and drying to obtain the scaffold. The electroactive micron/nanometer fiber scaffold prepared by the invention has stable conductivity and good biocompatibility required by electro-stimulation on cells, and well avoids direct contact between the conductive high-polymer and a cell culture solution or an organism at the same time, so that the problem of instable conductivity caused by de-doping is solved, and the scaffold has a very good practical value in the aspect of nerve tissue engineering (see abstract).
3. DeMattei et al.
DeMattei et al. teach delivery of biologically active materials using core-shell
tecto(dendritic polymers) (see title). Additionally, DeMattei et al. disclose that the present invention concerns core-shell tecto (dendritic polymers) that are associated with biologically active materials (such as nucleic acids for use for RNAi and in transfection).
Also included are formulations for their use. The constructs are useful for the delivery of drugs to an animal or plant and may be in vivo, in vitro or ex vivo (see abstract).
4. Park et al.
Park et al. teach electroconductive fiber, a fiber complex including an
electroconductive fiber and methods of manufacturing the same (see title). Also, Park et al. disclose an electroconductive fiber, a method of manufacturing an electroconductive fiber, and a fiber complex including an electroconductive fiber are provided. The electroconductive fiber includes an electroconductive polymer, an elastic polymer
that forms a structure with the electroconductive polymer, and a carboneous material on at least one of the electroconductive polymer and the elastic polymer (see abstract).
5. Reches et al.
Reches et al. teach peptide nanostructures containing end-capping modified peptides and methods of generating and using the same (see title). Furthermore, Reches et al. disclose a nanostructure composed of a plurality of peptides, each peptide containing at least one aromatic amino acid, whereby one or more of these peptides is end-capping modified, is disclosed. The nanostructure can take a tubular, fibrillar, planar or spherical shape, and can encapsulate, entrap or be coated by other materials. Methods of preparing the nano structure, and devices and methods utilizing same are also disclosed (see abstract).
6. Mohanty et al.
Mohanty et al. teach functional wound healing dressings (see title). Additionally, Mohanty et al. disclose that one aspect of the present disclosure relates to the use of vitrified active agents such as growth factors and/or one or more antimicrobial peptides (AMPs), or other desired active agent, for wound healing as a component of a wound dressing whereby the active agents are vitrified onto one or more polymeric materials, and their release rate regulated by the presence of one or more biodegradable polymeric materials (see abstract).
Combination of Serrano-Garcia et al., Yu, and DeMattei et al.
Regarding instant claim 1, Serrano-Garcia et al., Yu, and DeMattei et al. teach an ex vivo method for delivering bioactive cargo to cells, comprising exposing the cells and bioactive cargo to electrospun core-shell fibers. The necessary citations of Serrano-Garcia et al., Yu, and DeMattei et al. that pertain to instant claim 1 are presented in Table I.
Table I
Instant Claim 1
Serrano-Garcia et al., Yu, and DeMattei et al. Citations
An ex vivo method for delivering bioactive cargo to cells, comprising exposing the cells and bioactive cargo to electrospun core-shell fibers that comprise:
Serrano-Garcia et al. teach a coaxial nanocomposite including a core, which includes fibers of a first organic polymer, and a shell, which includes fibers of a second organic polymer, the first polymer and the second polymer forming a heterojunction (see abstract within Serrano-Garcia et al.). Intelligent textiles, air/water filters, bone scaffolds, and drug delivery applications have all directly benefitted from the reliable and low-cost electrospinning technique for fiber fabrication (see paragraph [0005] within Serrano-Garcia et al.). The internal core also can be inclusive of two or more organic semiconducting fibers having the composition of blended or distinct polymers. If the internal separation of core nanofibers is larger than 0, a multicore coaxial fiber is created. The core strands can be from the same or different organic semiconductive or conductive polymers (see paragraph [0025] within Serrano-Garcia et al.).
Yu discloses an electrospun core-shell fiber comprising:
(i) a central core that is electrically conductive having an exterior surface, wherein the core comprises a first electroconductive material polymeric material;
(ii) a shell adjacent to the exterior surface of the core, the shell comprising a second polymer; (see claim 1; and paragraphs [0007] and [0008-0018] within Yu)
The core-shell fibers are ideal for drug, gene and cell delivery (see paragraph [0005] within Yu), the conductive polymer of the core is selected among polypyrrole or polyaniline (see paragraph [0011] within Yu) and the biodegradable polymer is selected from PLA, spider silk protein, silk fibroin (see paragraph [0014] within Yu). The fibers present pores and voids (see paragraph [0018] within Yu).
DeMattei et al. disclose delivering bioactive cargo to cells ex vivo (see the abstract disclosing "The present invention concerns core-shell tecto (i.e. dendritic polymers) that are associated with biologically active materials…The constructs are useful for the delivery of drugs to an animal or plant and may be in vivo, in vitro or ex vivo”; also see claims 32-34, 40 and 48 within DeMattei et al.)
(i) a central core that is electrically conductive having an exterior surface, wherein the core comprises a first polymer and an electroconductive material;
(ii) a shell adjacent to the exterior surface of the core, the shell comprising a second polymer;
and (iii) one or more bioactive agents in the shell.
Therefore, a skilled artisan (POSITA; person of ordinary skill in the art) would consult the disclosures of Serrano-Garcia et al., Yu, and DeMattei et al. to teach all the elements of instant claim 1.
The remainder of the instant claims which are either directly dependent on claim 1 are taught in full by the combination of Serrano-Garcia et al., Yu, and DeMattei et al.
Regarding instant claim 2, Serrano-Garcia et al., Yu, and DeMattei et al. teach wherein the exposure occurs in the presence of an electric field. Yu discloses wherein the exposure occurs in the presence of an electric field (see paragraph [0021-0022] within Yu). Also, Serrano-Garcia et al. disclose wherein the exposure occurs in the presence of an electric field (preparation; see paragraphs [0047-0051].
Regarding instant claim 3, Serrano-Garcia et al., Yu, and DeMattei et al. teach wherein the cells are pre-adhered to a culture vessel, and wherein the electrospun core-shell fibers are introduced into the vessel. Yu discloses wherein the cells are pre-adhered to a culture vessel, and wherein the electrospun core-shell fibers are introduced into the vessel (in vitro; see paragraph [0021-0022] within Yu).
Regarding instant claim 4, Serrano-Garcia et al., Yu, and DeMattei et al. teach wherein the cells are adhered to the electrospun core-shell fibers. Yu discloses wherein the cells are adhered to the electrospun core-shell fibers (see paragraph [0021-0022] and Figure 3; both within Yu).
Regarding instant claim 6, Serrano-Garcia et al., Yu, and DeMattei et al. teach wherein the electroconductive polymer comprises polyaniline, polyaniline, a poly(pyrrole), an oxidized polyacetylene, a poly(fluorene), a polyphenylenes, a polypyrene, a polyazulene, a polynaphthalene, a poly(p-phenylene vinylene), a polycarbazole, a polyindoles, a polyazepine, a poly(thiophene), a poly(3,4-ethylenedioxythiophene), a poly(p-phenylene sulfide), a poly(naphthalene vinylene), a poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate), a poly(3,4-ethylenedioxythiophene)-block-poly(ethylene glycol), or any combination thereof. Yu discloses wherein the conductive polymer is polypyrrole or polyaniline (see claim 1 and paragraph [0024]; both within Yu). A skilled artisan (POSITA) would be able to combine the two conductive polymers under routine experimental conditions.
Regarding instant claim 8, Serrano-Garcia et al., Yu, and DeMattei et al. teach wherein the weight ratio of the first polymer to the electroconductive polymer is from 2:1 to 1:2. Yu discloses wherein the weight ratio of the first polymer to the electroconductive polymer is from 2:1 to 1:2 (0.12 wt% polymer:0.10 wt% conductive polymer; ~1:1; see paragraphs [0007-0010] within Yu). Additionally, Serrano-Garcia et al. teach in certain embodiments, the solution concentration of polystyrene (PS) prior to electro spinning may be from about 5 wt% to about 10 wt%, such as about 7 wt%. A concentration of PS less than about 7 wt % or less than about 5 wt % may be suitable for producing fibers with a beaded structure (i.e., pendants, beaded). A concentration of PS greater than 7 wt% or greater than 10 wt% may be suitable for producing agglomerated fibers or films. In certain embodiments, the solution concentration of P3HT (electroconductive agent) prior to electro spinning may be from about 0.1 wt% to about 2.0 wt%, such as 0.4 wt%. However, a concentration of about 2.0 wt % may significantly increase the electrical charge of the solution and other electrospinning parameters may need to be adjusted accordingly. In certain embodiments, the amount of PS present in the nanocomposite may be from about 6 wt % to about 8 wt %, such as about 7 wt %. Alternately, the amount of PS may be less than 6 wt %, particularly when the molecular weight is greater. (see paragraph [0043] within Serrano-Garcia et al.). When P3HT (electroconductive polymer) is about 2% and PS (1st polymer) is about less than 6%, which could be 4% or 2%. The ratio of the PS polymer: P3HT (electroconductive polymer) would be 2:1 or 1:1.
Regarding instant claims 13-16 and 18-21, Serrano-Garcia et al., Yu, and DeMattei et al. teach wherein the first polymer is biocompatible. Serrano-Garcia et al. disclose the use of the biodegradable polymers polystyrene (PS) and polylactic acid (PLA) (see paragraph [0033] within Serrano-Garcia et al.). Furthermore, Yu discloses the use of the biodegradable polymer PLA and the natural polymers spider silk or silk with desiccant (see claim 1 within Yu). In addition, the use of the above natural polymers by Yu enables a skilled artisan (POSITA) to expand this list and use common natural polymers such as collagen, gelatin, or chitosan or combinations thereof (see PTO-892 NPL V).
Regarding instant claims 17 and 24, Serrano-Garcia et al., Yu, and DeMattei et al. teach wherein the core has an average diameter of about 100 nm to about 20 mm and wherein the shell has a thickness of about 10 nm to about 20 mm. Serrano-Garcia et al. disclose wherein the core diameter may be from about 150 nm to about 250 nm, such as about 194 nm, about 200 nm, or about 225 mn. In other embodiments, the core diameter may be greater than 200 nm, such as about 435 nm, about 713 nm, about 1390 nm, or about 2772 nm (see paragraph [0042] within Serrano-Garcia et al.). Serrano-Garcia et al. disclose the shell diameter may be from about 25 nm to about 75 nm, such as about 30 nm, about 31 nm, or about 55 nm. In other embodiments, the shell diameter may be greater than 75 nm, such as about 327 nm, about 520 nm, about 552 nm, about 605 nm, or about 1652 nm (see paragraph [0042] within Serrano-Garcia et al.).
Regarding instant claims 22 and 23, Serrano-Garcia et al., Yu, and DeMattei et al. teach wherein the first polymer and the second polymer are the same polymer and/or different polymers. Serrano-Garcia et al. and Yu disclose both natural and synthetic biodegradable polymers (see instant claims 13-16 and 18-21). A skilled artisan (POSITA) would be able to select either the same or different polymers from the biodegradable molecules.
Regarding instant claim 27, Serrano-Garcia et al., Yu, and DeMattei et al. teach wherein the active ingredient is a polypeptide, a small molecule, a vaccine, vesicles isolated from cells that have been reprogrammed, and any combination thereof. DeMattei disclose examples of such biologically active materials include, but are not limited to, pro-drugs, pharmaceuticals, small organic molecules, and biomolecules. Additionally these core-shell tecto(dendritic polymers) of Formula I may be formulated with usual excipients, and other inert ingredients for administration (see paragraph [0122] within DeMattei et al.).
Combination of Serrano-Garcia et al., Yu, DeMattei et al., and Park et al.
Regarding instant claims 5 and 12, Serrano-Garcia et al., Yu, DeMattei et al., and Park et al. teach wherein the electroconductive material comprises an electroconductive polymer, an electroconductive metal, or a combination thereof. Yu discloses wherein the electroconductive material comprises an electroconductive polymer (see instant claim 6). Park et al. disclose wherein the electroconductive material comprises an electroconductive metal (see paragraph [0070] within Park et al.). Therefore, a skilled artisan (POSITA) could combine these two electroconductive materials under routine experimental conditions within the central core of the electrospun fibers.
Regarding instant claim 9, Serrano-Garcia et al., Yu, DeMattei et al., and Park et al. teach wherein the electroconductive metal comprises tantalum, gold, niobium, silver, copper, aluminum, iron, zinc, molybdenum, lithium, nickel, palladium, platinum, tungsten, tin, rhodium, iridium, or any combination thereof. Park et al. disclose wherein the electroconductive material comprises an electroconductive metals such as silver, copper, nickel, gold, tin, zinc, platinum, tungsten, molybdenum or mixtures thereof (see paragraph [0070] within Park et al.).
Regarding instant claim 10, Serrano-Garcia et al., Yu, DeMattei et al., and Park et al. teach wherein the electroconductive metal comprises a plurality of metal nanoparticles. Park et al. disclose wherein the electroconductive metal comprises a plurality of metal nanoparticles (see paragraph [0014] within Park et al.).
Regarding instant claim 11, Serrano-Garcia et al., Yu, DeMattei et al., and Park et al. teach wherein the weight ratio of the first polymer to the electroconductive metal is from 1:10 to 1:1. Park et al. disclose a polymer range of 0.05-40% by weight, and an electroconductive metal level range of 0.05-5% by weight (see paragraphs [0084-0085] and [0088]; all within Park et al.). Therefore, these weight percent values produce overlapping ranges with the instant claim 11 limitation and the Park et al. citation.
Combination of Serrano-Garcia et al., Yu, DeMattei et al., and Reches et al.
Regarding instant claim 25, Serrano-Garcia et al., Yu, DeMattei et al., Reches et al. teach wherein the shell comprises a plurality of nanochannels. Reches et al. disclose the use of both a microchannel and a nanochannel (see page 16, line 25 within Reches et al.).
Regarding instant claim 26, Serrano-Garcia et al., Yu, DeMattei et al., Reches et al. teach wherein the nanochannels have an average diameter of about 10 nm to about 1,000 nm. Reches et al. disclose channel 84 is preferably in a micrometer size (i.e., a microchannel) or a nanometer size (i.e., a nanochannel), both are known in the art. In the embodiment in which channel 84 is a nanochannel, the diameter thereof is larger than the diameter of the largest nanostructure, so as to allow nanofluid 82 to flow freely through channel 84 (see page 73, lines 5-9; and Figure 12; both within Reches et al.). [By definition a nanochannel is less than 1 mm in diameter.]
Regarding instant claim 29, Serrano-Garcia et al., Yu, DeMattei et al., Reches et al. teach wherein the fibers are continuous. Reches et al. disclose wherein the fibers are continuous (see page 71, lines 26-32 within Reches et al.).
Combination of Serrano-Garcia et al., Yu, DeMattei et al., and Mohanty et al.
Regarding instant claim 28, Serrano-Garcia et al., Yu, DeMattei et al., and Mohanty et al. teach wherein the one or more bioactive agents comprise one or more of genes such as LL37, laminin/collagen VII, and VEGF/EGF. Mohanty et al. disclose wherein the one or more bioactive agents comprise genes such as LL37 (see paragraph [0064] within Mohanty et al.). A skilled artisan (POSITA) could expand the bioactive agents to include either/or laminin/collagen VII and VEGF/EGF depending upon the biological target and desired treatment within the subject.
Analogous Art
The Serrano-Garcia et al., Yu, DeMattei et al., Park et al., Reches et al., and Mohanty et al. references are directed to the same field of endeavor as the instant claims, that is, an ex vivo method for delivering bioactive cargo to cells, comprising exposing the cells and bioactive cargo to electrospun core-shell fibers as disclosed within instant claim 1.
Obviousness Analysis
It would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to modify the semiconductive organic nanofibers disclosed by Serrano-Garcia et al., using the teachings of Yu, DeMattei et al., Park et al., and further in light of the claim-specific feature described in Reches et al. and Mohanty et al. in order to arrive at the subject matter of the instant claims.
The Serrano-Garcia et al., Yu, DeMattei et al., Park et al., Reches et al., and Mohanty et al. references all have considerable overlap for electrospun core-shell fibers comprising bioactive cargo. In this instance, Serrano-Garcia et al. and Yu supplies the overall preparation process for the electrospun core-shell fibers, DeMattei et al. supplies the bioactive cargo, Park et al. supplies the metal nanoparticles, while Reches et al. and Mohanty et al. supply claim-specific features comprising nanochannels and additional bioactives, respectively. All references are directed to electrospun core-shell fibers comprising bioactive cargo and therefore constitute analogous art under MPEP §2141.01(a). A POSITA would have reasonably consulted the six references when seeking to develop a method for delivery of electrospun core-shell fibers comprising bioactive cargo.
Starting with Serrano-Garcia et al., the skilled person only had to try the necessary claim limitations disclosed by Yu, DeMattei et al., Park et al., Reches et al., and Mohanty et al. The combination of Serrano-Garcia et al., Yu, DeMattei et al., Park et al., Reches et al., and Mohanty et al. would allow one to arrive at the present application without employing inventive skill. This combination of the semiconductive organic nanofibers taught by Serrano-Garcia et al. along with the use of the necessary claim limitations taught by Yu, DeMattei et al., Park et al., Reches et al., and Mohanty et al. would allow a research and development scientist (POSITA) to develop the invention taught in the instant application. It would have only required routine experimentation to modify the semiconductive organic nanofibers disclosed by Serrano-Garcia et al. with the use of the necessary claim limitations taught by Yu, DeMattei et al., Park et al., Reches et al., and Mohanty et al. Incorporating the disclosure of Serrano-Garcia et al. into the electrospun core-shell fibers comprising bioactive cargo taught by Yu, DeMattei et al., Park et al., Reches et al., and Mohanty et al. represents a predictable use of prior art elements according to their established functions, consistent with MPEP §2143 and KSR.
Furthermore, the additional claim limitations taught by Yu, DeMattei et al., Park et al., Reches et al., and Mohanty et al. would have been viewed by a POSITA as routine design optimizations or known modifications for electrospun core-shell fibers comprising bioactive cargo. Implementing these features in Serrano-Garcia et al.’s semiconductive organic nanofibers would not require more than ordinary skill or routine experimentation.
Accordingly, the combination of Serrano-Garcia et al., supplemented by Yu, DeMattei et al., Park et al., Reches et al., and Mohanty et al. provides all the elements of the claimed invention. The resulting electrospun core-shell fibers comprising bioactive cargo constitutes no more than the predictable outcome of combining familiar prior art components, and therefore the claimed subject matter would have been obvious to a POSITA prior to the effective filing date of the invention.
Conclusion
No claims are allowed.
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/JOHN W LIPPERT III/Examiner, Art Unit 1615 /Robert A Wax/Supervisory Patent Examiner, Art Unit 1615