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 .
Election/Restriction
REQUIREMENT FOR UNITY OF INVENTION
As provided in 37 CFR 1.475(a), a national stage application shall relate to one invention only or to a group of inventions so linked as to form a single general inventive concept (“requirement of unity of invention”). Where a group of inventions is claimed in a national stage application, the requirement of unity of invention shall be fulfilled only when there is a technical relationship among those inventions involving one or more of the same or corresponding special technical features. The expression “special technical features” shall mean those technical features that define a contribution which each of the claimed inventions, considered as a whole, makes over the prior art.
The determination whether a group of inventions is so linked as to form a single general inventive concept shall be made without regard to whether the inventions are claimed in separate claims or as alternatives within a single claim. See 37 CFR 1.475(e).
When Claims Are Directed to Multiple Categories of Inventions:
As provided in 37 CFR 1.475 (b), a national stage application containing claims to different categories of invention will be considered to have unity of invention if the claims are drawn only to one of the following combinations of categories:
(1) A product and a process specially adapted for the manufacture of said product; or
(2) A product and a process of use of said product; or
(3) A product, a process specially adapted for the manufacture of the said product, and a use of the said product; or
(4) A process and an apparatus or means specifically designed for carrying out the said process; or
(5) A product, a process specially adapted for the manufacture of the said product, and an apparatus or means specifically designed for carrying out the said process.
Otherwise, unity of invention might not be present. See 37 CFR 1.475 (c).
Restriction is required under 35 U.S.C. 121 and 372.
This application contains the following inventions or groups of inventions which are not so linked as to form a single general inventive concept under PCT Rule 13.1.
In accordance with 37 CFR 1.499, applicant is required, in reply to this action, to elect a single invention to which the claims must be restricted.
Group I, claims 1-7, drawn to a bioactive implant for restoring the conductivity of the bioelectrical stimuli in cardiac tissue.
Group II, claims 8-12, drawn to a method for manufacturing a bioactive implant for restoring the conductivity of the bioelectrical stimuli in cardiac tissue.
The groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons:
Groups I and II lack unity of invention because even though the inventions of these groups require the technical feature of a polymeric matrix of silk fibroin in aqueous solution previously electrospun with a polar sacrificial polymer, reinforced with a gold nanoparticle membrane synthetized with silk fibroin, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Akturk et al “Wet electrospun silk fibroin/gold nanoparticle 3D matrices for wound healing applications”; RSC Advances, 2016, 6, 1323-13250. Akturk discloses a polymeric matrix of silk fibroin in aqueous solution (see Akturk, page 13235, column 2, Fabrication of Scaffolds, lines 1-4) previously electrospun with a polar sacrificial polymer (see Akturk, page 13325, column 2, Fabrication of Scaffolds, lines 12-15 discloses a polar sacrificial polymer, page 13326, first column, Wet Elecrospinning discloses electrospinning)), reinforced with a gold nanoparticle membrane synthetized with silk fibroin (see Akturk, page 13325, Synthesis of gold nanoparticles discloses gold nanoparticles, page 13326, column 1, lines 5-9 discloses reinforcing the silk fibroin scaffold) . The product of claims 1-7 can be manufactured by steps that are different than the step required in the manufacturing method of claims 8-12, therefore, the product and process claims are not linked to form a single general inventive concept.
During a telephone conversation with applicant’s representative, Jospeh Morales, on 01/21/2026 a provisional election was made without traverse to prosecute the invention of Group II, claims 8-12. Affirmation of this election must be made by applicant in replying to this Office action. Claims 1-7 withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Claim Objections
Claims 8-12 are objected to because of the following informalities:
Claims 9-12 are dependent on claim 7, however, claim 7 is not a method to manufacture the bioactive implant. Examiner suggests amending the claims to depend from claim 8. The examiner has interpreted claims 9-12 to be dependent on claim 8 for antecedent purposes.
Claim 8, lines 3-4 state “4,5 – 5%”, examiner suggests amending the claim to read “4.5 – 5%”.
Claim 8, line 6 states “0,3 – 0,6%”, examiner suggests amending the claim to read “0.3 – 0.6%”.
Claim 8, line 12 states “3,5 – 4,5%”, examiner suggest amending the claim to read “3.5 – 4.5%”.
Claim 9, lines 3-4 states “2 – 2,5 mM”, examiner suggests amending the claim to read “2 – 2.5 mM”.
Claim 10, line 3 states “0,1 N”, examiner suggests amending the claim to read “0.1 N”.
Claim 8, lines 16-17 state “immerse the electrospun matrix in a solution of organic solvent selected from the methanol, ethanol, …”, the examiner suggests amending the claim to read “immerse the electrospun matrix in a solution of organic solvent selected from the group consisting of methanol, ethanol, …”.
Claim 8, line 20 states “vaccum”, examiner suggests amending the claim to read “vacuum”.
Appropriate correction is required.
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 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.
Claims 8-9, and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Kaplan et al (WO 2014/021954 A1) in view of Akturk et al (“Wet electrospun silk fibroin/gold nanoparticle 3D matrices for wound healing applications”; RSC Advantages (2016),6,13234-13250) in view of Kaplan et al (US 2010/0196447 A1).
Regarding claim 8, Kaplan ‘954 discloses a method for manufacturing a bioactive implant (see Kaplan ‘954, paragraph 0015) for restoring the conductivity of the bioelectrical stimuli in cardiac tissue (see Kaplan ‘954, paragraph 00167) comprising the following stages:
-Provide silk fibroin in aqueous solution (see Kaplan ‘954, paragraph 0097; paragraph 0050 of Kaplan ‘954 discloses that Zhang et al WO 2011/008842 is incorporate by reference, paragraph 0051 of Zhang discloses silk fibroin in an aqueous solution) at a concentration between 4.5-5% vol/vol (paragraph 0051 of Zhang discloses blend solution of SF/PEO, the silk fibroin concentration in w/v is 8% w/v which represents 8 g SF/100 mL of aqueous solution, SF density ≈ 1.3 g/ml, 8% w/v SF = 6.15% vol/vol SF, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to provide 4.5-5% vol/vol of silk fibroin to the aqueous solution because paragraph 0051 of Zhang discloses that the initial blending ratio between silk fibroin protein and PEO may depend on the viscoelastic and surface tension properties desired to generate stable fluid jets during electro spinning, therefore it is disclosed to be a result effective variable in that changing the concentration of the silk fibroin effects the formulation of a material that produces stable, continuous spinning. Modifying the silk fibroin concentration of Kaplan would be a matter of routine optimization since it has been held that “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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)).
-synthetize gold nanoparticles in a silk fibroin aqueous solution at a concentration between 0.3 -0.6% vol/vol (see Kaplan ‘954, paragraph 0066 discloses 0.3-0.6% vol/vol of the magnetic particles can be distributed or embedded homogenously or heterogeneously within a silk fibroin-based material; paragraph 0079 discloses that the magnetic particles can be gold nanoparticles);
-mix the silk fibroin solution with a polar sacrificial polymer selected from the group consisting of polyethylene oxide (PEO), poly (ethylene glycol) (PEG), poly (vinyl alcohol) (PVA), poly (vinyl pyrrolidone (PVP), polylactic acid (PLA), polyglycolic acid (PGA), polylactic-co-glycolic acid (PLGA), poly (L-lactide-co-e-caprolactone) (paragraph 0050 of Kaplan ‘954 discloses mixing the silk fibroin solution with a polar sacrificial polymer), where the polar sacrificial polymer is in a concentration between 3.5 – 4.5% m/vol (paragraph 0050 of Kaplan ‘954 discloses a varying range of %wt for the SF/PEO blend, where the range of %wt PEO would encompass 3.5-4.5% m/vol, additionally, as stated above paragraph 0050 of Kaplan ‘954 incorporates by reference Zhang et al WO 2011/008842, paragraph 0051 of Zhang discloses that the initial blending ratio between silk fibroin protein and PEO may depend on the viscoelastic and surface tension properties desired to generate stable fluid jets during electro spinning, therefore it is disclosed to be a result effective variable in that changing the concentration of the silk fibroin effects the formulation of a material that produces stable, continuous spinning Modifying the silk fibroin concentration of Kaplan would be a matter of routine optimization since it has been held that “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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955));
-mix the silk fibroin solution and the polar sacrificial polymer (paragraphs 0012 and 0050 of Kaplan ‘954 discloses the silk fibroin solution and the polar sacrificial polymer) with the gold nanoparticles (paragraph 0079 discloses gold nanoparticles; paragraph 0066 discloses they can be heterogenously or bomogenously distributed or embedded within the silk fibroin material);
-the mix obtained is subject to electrospinning through sequential rotary electrospinning (see Kaplan ‘954, paragraph 0119-0120; paragraph 0146 discloses sequential rotary electrospinning);
-immerse the electrospun matrix in a solution of organic solvent selected from the methanol, ethanol, propanol, butanol, glutaraldehide (GA), acetone group (see Kaplan ‘954, paragraph 00145);
-obtain the bioactive implant (see Kaplan ‘954, abstract).
Kaplan discloses mixing the silk fibroin solution and the polar sacrificial polymer with the gold nanoparticles, however, Kaplan does not specifically disclose mixing the silk fibroin solution and the polar sacrificial polymer with the synthetized gold nanoparticle solution.
Akturk discloses a synthetized gold nanoparticle solution (see Akturk, page 13235, Synthesis of Gold Nanoparticles) mixed with silk fibroin solution and the polar sacrificial polymer (see AKturk, page 13236, column 1, lines 5-9).
It would have been obvious to a person having ordinary skill in the art before the effective filing date to modify the gold nanoparticles of the combination by providing a synthetized gold nanoparticle solution, as taught by Akturk, because using natural and biocompatible reducing/capping agents such as gelatin, collagen, silk fibroin, and plant extracts for the green synthesis of AuNPs might alleviate the cytotoxicity and so the incorporation extent of AuNPs into scaffolds could be increased more safely (see Akturk, page 13243, column 2, lines 25-29).
As set forth supra, the combination does not specifically disclose placing the implant in a controlled vaccum atmosphere for 20-24; and washing with deionized water.
Kaplan ‘447 discloses a preparation method for a silk fibroin/polymer implant (see Kaplan ‘447, abstract) wherein the method teaches placing the implant in a controlled vacuum atmosphere for 20-24 h (see Kaplan ‘447; paragraph 0086 “The films then placed vacuum for another 24 hrs.”); and washing with deionized water (see Kaplan ‘447, paragraph 0086 “After crystallizing the silk and silk/PEG or PEO blends using methanol, their solubility in water, 17 M.OMEGA. at 37.degree. C., was determined for 48 hrs”).
It would have been obvious to a person having ordinary skill in the art before the effectively filing date of the claimed invention to modify the method of the combination by placing the implant in a controlled vacuum atmosphere for 20-24; and washing with deionized water as taught by Kaplan ‘447 because the use of the technique of placing the implant in a controlled vacuum atmosphere for 20-24; and washing with deionized water as taught by Kaplan ‘447 in the invention of the combination would have comprised only application of a known technique to a known device ready for improvement to yield the predictable result of dissolving the sacrificial polymer (see Kaplan ‘447, paragraph 0086); and similar modifications have previously been held to involve only routine skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007).
Regarding claim 9, as set forth supra, the combination discloses the invention substantially as claimed.
However, the combination does not disclose wherein the implant is characterized because in the synthesis stage of gold nanoparticles, the silk fibroin solution is mixed with a chloroauric solution (HAuCl4) at a concentration between 2 – 2.5 mM.
Akturk discloses a method for manufacturing a silk fibroin/PEO implant (see Akturk, abstract) and a synthesis stage of gold nanoparticles (see Akturk, page 13235, column 2, Synthesis of Gold Nanoparticles) wherein the silk fibroin solution is mixed with a chloroauric solution (HAuCl4) (see Akturk, page 13235, column 2, Synthesis of Gold Nanoparticles, lines 1-4).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to mix the chloroauric solution (HAuCl4) as taught by Akturk because the chIoroauric solution is a known method which allows for the synthesis of gold nanoparticles which could be incorporated into the scaffold (see Akturk, page 13235, Synthesis of Gold Nanoparticles). This results in gold nanoparticles which are larger than 20 nm size and with a concentration below 20 ppm which were nontoxic on HaCat keratinocytes and 3T3 fibroblasts for at least 1 week period (see Akturk, page 13243, Cytotoxicity of Scaffold extracts, lines 8-12). Akturk does not specifically disclose wherein the chloroauric solution (HAuCl4) at a concentration between 2 – 2.5 mM, however, it would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the concentration of the chloroauric solution because the concentration of the solution is disclosed to be a result effective variable in that changing the concentration of the chloroauric solution effects the amount of gold nanoparticles present in the solution. Modifying the chloroauric solution of Akturk would be a matter of routine optimization since it has been held that “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." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Additionally, the applicant’s specification does not provide criticality for the concentration of the cloroauric solution.
Regarding claim 11, as set forth supra, the combination discloses a needle-collector distance between 15 and 20 cm (see Kaplan ‘954, paragraph 0127).
However, the combination is silent regarding wherein the electrospinning is carried out at a rotor speed from 50 to 250 rpm.
Akturk discloses a method for manufacturing a silk fibroin/PEO implant (see Akturk, abstract) regarding wherein the electrospinning is carried out at a rotor speed from 50 to 250 rpm (see Akturk, page 13236, Wet electrospinning, lines 1-6).
It would have been obvious to a person having ordinary skill in the art before the effective filing date of the claimed invention to modify the rotor speed of the combination by providing wherein the electrospinning is carried out at a rotor speed from 50 to 250 rpm as taught by Akturk because the use of the techniques of electrospinning at 50 to 250 rpm taught by Akturk in the invention of the combination would have comprised only application of a known technique to a known device ready for improvement to yield the predictable result of providing electrospun scaffolds; and similar modifications have previously been held to involve only routine skill in the art. KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007).
Regarding claim 12, as set forth supra, the combination discloses wherein the implant is characterized because in the washing stage, the deionized water is at 37°C, for 45 – 48 h (see Kaplan ‘447, paragraph 0086).
Allowable Subject Matter
Claim 10 is objected to as being dependent upon a rejected base claim, but would be allowable if: (1) rewritten in independent form including all of the limitations of the base claim and any intervening claims; and (2) Claims 9-12 are rewritten to overcome the claim objections set forth in this office action.
The following is an examiner' s statement of reasons for allowance:
The closest prior art of record is Kaplan et al (WO 2014/021954 A1) in view of Akturk et al (“Wet electrospun silk fibroin/gold nanoparticle 3D matrices for wound healing applications”; RSC Advantages (2016),6,13234-13250) in view of Kaplan et al (US 2010/0196447 A1) as stated above, however, the combination does not teach or render obvious the cumulative claim limitations wherein the synthesis stage of the gold nanoparticles includes a pH adjustment stage to a value between 9 – 10 with 0.1 N sodium dioxide and incubation under white light for 20 – 24 h at 32 – 34°C as recited in claim 10 within the context of the cumulative claim limitations.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA LYNEE ZIMMERMAN whose telephone number is (313)446-4864. The examiner can normally be reached Mon. 8:30 AM-6:30 PM, Tues. - Fri. 8:30-4:00 PM.
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/REBECCA LYNEE ZIMMERMAN/Examiner, Art Unit 3774
/SARAH W ALEMAN/Primary Examiner, Art Unit 3774