DETAILED ACTION
Claims 1-3, 5-12, and 14-23 are pending. Of these, claims 3, 8-9, and 18-23 are withdrawn as directed to a nonelected invention. Therefore, claims 1-3, 5-12, and 14-17 are under consideration on the merits.
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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restriction
Applicant’s election of Group I is acknowledged. Since Applicant did not point to any alleged deficiencies in the restriction requirement, the election has been treated as having been made without traverse. The restriction requirement is still considered proper and is made FINAL.
Applicant’s election of polycaprolactone as the species of synthetic polymer, a combination of chloroform and trifluoroethanol as the solvent, ceramic as the species of particles, and collagen as the species of biomolecule of claim 11, is acknowledged. Since Applicant did not point to any alleged deficiencies in the election of species requirement, the election has been treated as having been made without traverse. The election of species requirement is still considered proper and is made FINAL.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 2/5/24 and 6/22/26 was filed prior to the mailing date of a first Action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, it was considered by the Examiner.
Claim Objections
Claim 11 is objected to because of the following informalities:
The claim recites “ECM” without defining this term. The first appearance of an abbreviation in the claims should be accompanied by the fully spelled out term for clarity. Correction is required.
Claim 14 is objected to because of the following informalities:
The claim recites “SDF-1” without defining this term. The first appearance of an abbreviation in the claims should be accompanied by the fully spelled out term for clarity. Correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-3, 5-12, and 14-17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “the final solvent mixture,” but there is no antecedent basis for this limitation. Clarification is required. Dependent claims 2-3, 5-12, 14-7 are also rejected since they do not clarify the point of confusion.
Claim 1 recites that the synthetic polymer and organic volatile solvent are “in the ratio of 1.8:10 to 6:10,” which is indefinite because it is unknown what type of ratio it is, e.g., is it a weight ratio? Clarification is required. For the purpose of examination in view of the prior art, this limitation has been interpreted as a weight ratio. Dependent claims 2-3, 5-12, 14-7 are also rejected since they do not clarify the point of confusion.
Claims 6 and 10 recite “the ceramic, metallic or polymeric particles,” claim 7 recites “the ceramic particles,” claim 8 recites “the metallic particles, and claim 9 recites “the polymeric particles,” but there is no antecedent basis for these limitations in base claim 1. Clarification is required.
Claims 6 and 11 recite “the surface” of the microfibrillar filaments, but there is no antecedent basis for this limitation in base claim 1. Clarification is required. Dependent claims 7 and 10 do not clarify the point of confusion so is also rejected.
Additionally, claim 11 recites “including” in line 3 and again in line 4, and “such as” in line 4, and the use of such exemplary language renders the metes and bounds of the claim unclear, because it is unknown whether the claim is requiring the presence of the species recited after the exemplary language. MPEP 2173.05(d). Clarification is required. For the purpose of examination in view of the prior art, the claim has been given its broadest reasonable interpretation, which is that the presence of the recited species is not a required element.
Claim 14 recites that the matrix is loaded with bioactive factors “such as” SDF-1 alpha. The use of “such as” renders the metes and bounds of the claim unclear, because it is unknown whether the claim is requiring the presence of SDF-1 alpha. MPEP 2173.05(d). Clarification is required. For the purpose of examination in view of the prior art, the claim has been given its broadest reasonable interpretation, which is that the presence of SDF-1 alpha is not a required element.
Claim 15 recites “the complex in vitro procedures,” but there is no antecedent basis for this limitation. Additionally, the metes and scope of this limitation is unclear. Neither the claim nor the specification defines what a “complex in vitro procedure” is in the context of the claim. Clarification 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 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 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 1-3, 5-7, 10, 12, and 15-17 are rejected under 35 U.S.C. 103 as unpatentable over (Arinzeh (US Pat. No. 9,181,636; issued 11.10.15) in view of Ghubayra (FABRICATION AND CHARACTERIZATION OF ELECTROSPUN POLY(ε- CARPOLACTONE) - BASED POLYMER BLEND FIBERS. Masters Dissertation dated October 2017).
As to claims 1-3, 5-7, 10, 12, and 15-17, Arinzeh discloses a matrix comprising a mesh of electrospun fibers (“microfibrillar filaments”) made from a polymeric solution comprising a synthetic polymer such as polycaprolactone (the elected species of synthetic polymer of claims 1-2) and an organic volatile solvent such as chloroform (one of the two solvents elected by Applicant in combination, i.e., chloroform and trifluoroethanol), although Arinzeh teaches that any solvent or combination of solvents generally useful to prepare a polymer solution may be used, including, for example, hexafluoroisopropanol (paragraph bridging columns 3-4 and 2nd full paragraph of column 11), the matrix further comprising ceramic particles such as tricalcium phosphate or hydroxyapatite of claims 6-7 (paragraph bridging columns 3-4 and column 12, 3rd full paragraph). Arinzeh discloses a specific embodiment wherein 10 ml (13.25 gm) of methylene chloride solvent is used to dissolve 2 grams of polymer, resulting in a weight ratio of about 1:6.6 that is slightly above the range recited by claim 1 which encompasses a weight ratio of 1.8:10, or the equivalent of about 1:5.6 (column 12, last full paragraph).
Regarding claim 5, the average pore size is at least 80 microns (claim 11 of Arinzeh), which overlaps the ranges of claim 5. Arinzeh does not distinguish between the pore size in a single plane and the size through the thickness of the membrane, so the range recited by Arinzeh is viewed as applicable to both instances.
Regarding claim 6, Arinzeh further teaches that the ceramic particles are incorporated by adding them to the polymer solution followed by electrospinning and evaporation of solvent, which will result in the particles being embedded within or on the surface of the microfibrillar filaments (paragraph bridging columns 12-13).
As to claim 10 the ceramic particles may have a particle size of about 100 nm, which is within the recited range (column 13, 1st paragraph).
As to claim 12, the diameter of the fibers may be 1-50 microns (column 13, 2nd full paragraph).
Regarding claims 15-17, these claims are directed to intended uses of the matrix and as such are not granted additional patentable weight. Arinzeh teaches that the matrix taught therein serves as a scaffold for cells for tissue repair and from which cells may attach and migrate (“Field of the Invention” at column 1 and column 7, 4th paragraph), and therefore is viewed as capable of carrying out the intended uses recited by claims 15-16 such as serving as a sleeve and pockets at a defective site for tissue regeneration or to support cell migration and vasculature generation, and also capable of serving as an encapsulating material to support floating of membranes or hydrogels loaded with drugs or bioactive factors for delivering into a liquid media or localized site (claim 17). .
As to claims 1-3, 5-7, 10, 12, and 15-17, Arinzeh does not further expressly disclose that the ratio of polymer to organic volatile solvent is within the range of claim 1 as discussed above or that the chloroform organic solvent is mixed with trifluoroethanol as elected by Applicant and wherein the chloroform makes up a minimum of 70% of the solvent mixture as recited by claim 1, or that the matrix pore size is enlargeable up to 8 times its original size stretching in a direction perpendicular to the longitudinal axis of the microfibrillar filaments so as to disperse the microfibrillar filaments without any tearing or failure of the matrix and wherein the microfibrillar filaments are parallelly aligned with minimum inter-fibrillar bonding within the range of from 0-400/cm2 with 0-60 degree overlap among the filaments as recited by claim 1, or that the solvent comprises trifluoroethanol in addition to the chloroform as required by Applicant’s species election.
Ghubayra discloses the fabrication of electrospun fibers comprising polycaprolactone, and teaches using a 1:1 mixture of chloroform and trifluoroethanol as the solvent for the electrospinning solution (Abstract on page iii).
As to claims 1-3, 5-7, 10, 12, and 15-17, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the electrospun scaffold of Arinzeh by selecting trifluoroethanol as the organic solvent solution in addition to the chloroform taught by Arinzeh, since Arinzeh expressly teaches that any solvent suitable for preparation of the polymer being electrospun may be used including combinations of solvents, and further lists hexafluoroisopropanol as an example, which is similar to trifluoroethanol in that it is a fluorinated lower alcohol, and Ghubayra teaches that a mixture of chloroform and trifluoroethanol can be used to produce electrospun fibers comprising polycaprolactone, such that the skilled artisan reasonably would have expected that such a solvent mixture could be used to form the electrospun polycaprolactone fibers of the Arinzeh matrix. Such a modification is merely the simple substitution of one known element for another according to known methods to yield predictable results, which is prima facie obvious. MPEP 2143.
Regarding the recitation of claim 1 that the matrix is made from a polymeric solution wherein the ratio of polymer to organic volatile solvent is within the recited range and the amount of chloroform is at least 70%, claim 1 is written in the form of a product by process claim, and as such its patentability is determined by the structure of the claimed composition and not the steps by which the composition is made. “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) (Claim was directed to a novolac color developer. The process of making the developer was allowed. The difference between the inventive process and the prior art was the addition of metal oxide and carboxylic acid as separate ingredients instead of adding the more expensive pre-reacted metal carboxylate. The product-by-process claim was rejected because the end product, in both the prior art and the allowed process, ends up containing metal carboxylate. The fact that the metal carboxylate is not directly added, but is instead produced in-situ does not change the end product.).
Here, the skilled artisan would recognize that the solvent is removed from electrospun fibers during the electrospinning process, such that the structure of the electrospun matrix of Arinzeh and Ghubayra as combined supra will be the same or substantially the same as the electrospun fibers of the present claims based upon the evidence of record. Additionally, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985)(Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). Here, the ratio of about 1:6.6 disclosed by Arinzeh is sufficiently similar to the claimed ratio range which encompasses a weight ratio of about 1:5.6 as discussed above, that the skilled artisan reasonably would have expected that the the solvent solution of Arinzeh and the fibers that are electrospun from the solvent solution, would have the same properties as the organic solvent solution recited by the claims and the fibers that are electrospun from them. Additionally, discovering optimum or working ranges involves only routine skill in the art in cases where the general conditions of a claim are disclosed in the prior art. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
The resulting matrix will have a pore size that is enlargeable up to 8 times its original size stretching in a direction perpendicular to the longitudinal axis of the microfibrillar filaments so as to disperse the microfibrillar filaments without any tearing or failure of the matrix and wherein the microfibrillar filaments are parallelly aligned with minimum inter-fibrillar bonding within the range of from 0-400/cm2 with 0-60 degree overlap among the filaments as recited by claim 1, because it comprises the same ingredients structurally arranged in the same way recited by the claims, and a product cannot be separated from its properties. The U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the countless ways that an Applicant may present previously unmeasured characteristics. When the prior art appears to contain the same ingredients that are disclosed by Applicants' own specification as suitable for use in the invention, a prima facie case of obviousness has been established, and the burden is properly shifted to Applicants to demonstrate otherwise. See MPEP 2112.01.
Claim 11 is rejected under 35 U.S.C. 103 as unpatentable over Arinzeh (US Pat. No. 9,181,636; issued 11.10.15) in view of Ghubayra (FABRICATION AND CHARACTERIZATION OF ELECTROSPUN POLY(ε- CARPOLACTONE) - BASED POLYMER BLEND FIBERS. Masters Dissertation dated October 2017) as applied to claims 1-3, 5-7, 10, 12, and 15-17 above, and further in view of Das et al. (Materials Science & Engineering D 111 (2020) 110723).
The teachings of Arinzeh and Ghubayra are relied upon as discussed above, but Arinzeh does not further expressly disclose that the microfibrillar filaments are functionalized with biomolecules such as the elected species, i.e., collagen.
Das discloses electrospun scaffolds that have been surface-modified with collagen and fibronectin, and teaches that these proteins are important regulators of cellular behavior and regulate the functions of primary hepatocytes, and that the modified electrospun scaffolds are able to significantly enhance functional properties of liver cells such that the scaffold would be useful for in vitro culture of liver cells (Abstract and last paragraph of section 2.1).
It would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the electrospun scaffold of Arinzeh and Ghubayra as combined supra by functionalizing the surface of the scaffold with collagen and fibronectin, because Das teaches that doing so will result in a scaffold that can support the functional properties of liver cells such that the scaffold would be useful to culture liver cells.
Claim 14 is rejected under 35 U.S.C. 103 as unpatentable over (Arinzeh (US Pat. No. 9,181,636) in view of Ghubayra (FABRICATION AND CHARACTERIZATION OF ELECTROSPUN POLY(ε- CARPOLACTONE) - BASED POLYMER BLEND FIBERS. Masters Dissertation dated October 2017) as applied to claims 1-3, 5-7, 10, 12, and 15-17 above, and further in view of Sun et al. (RSC Adv., 2019, 9, 25712).
The teachings of Arinzeh and Ghubayra are relied upon as discussed above, but Arinzeh does not further expressly disclose that the matrix is loaded with bioactive factors for imparting bioactivity.
Sun is a review of the use of electrospun fibers in biomedical fields including drug release and tissue repair (Abstract), and discloses that electrospun fibers have been used widely for disease treatment by loading a variety of drugs such as growth factors onto the fibers (last paragraph of page 25712).
It would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the electrospun fiber matrix of Arinzeh and Ghubayra as combined supra by loading an active substance such as a bioactive growth factor onto the matrix, because Sun discloses that electrospun fibers are useful for delivering drugs for treatment of disease when loaded with the drug such as a bioactive growth factor.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAREN GOTFREDSON whose telephone number is (571)270-3468. The examiner can normally be reached on M-F 9AM-6PM.
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/GAREN GOTFREDSON/Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner., Art Unit 1600
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