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 .
Priority
This application is a continuation-in-part of PCT Patent Application Serial No. PCT/US2023/028752, filed on July 26, 2023, which claims the benefit of U.S. Provisional Patent Application Serial No. 63/369,418, filed on July 26, 2022; and this application is also a continuation-in-part of U.S Patent Application Serial No. 16/910,051, filed on June 23, 2020, which is a continuation-in-part of PCT Patent Application Serial No. PCT/US2018/067427, filed on December 23, 2018, which claims the benefit of U.S. Provisional Patent Application Serial No. 62/610,155, filed on December 23, 2017.
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 01/18/2025, in the matter of Application N° 19/032,033. Said documents have been entered on the record.
Applicant’s CIP notably differs from the parent abandoned Application 16637137 by selecting “an L-valine-co-L-phenylalanine poly(ester urea)” in claim 2, which becomes the focus of this examination. Furthermore, with regard to the approach to the Application within this Office Action, compared to the approach for 16637137, “there is nothing unusual, certainly, about an examiner changing his viewpoint as to the patentability of claims as the prosecution of a case progresses, and so long as the rules of Patent Office practice are duly complied with an applicant has no legal ground for complaint because of such change in view. The life of a patent solicitor has always been a hard one. In re Ruschig, 154 USPQ 118, 120-21 (CCPA 1967).” However, the Examiner has attempted to maintain consistency from the earlier Application examinations.
The Examiner further acknowledges the following:
Claims 1-20 are pending.
Claims 1-20 are presented for examination and rejected as set forth below.
Drawings
The drawings are objected to because Figures 1(A-D) and Figures 3(A-D) contain very small font size (i.e., labels and/or axis) that appears pixelated in the uploaded file, and would likely be an issue for the USPTO Publication team.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 1-20 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being 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 term “about” to describe numerical values, which is indefinite because it is an imprecise definition of a value, which is not further defined in the Application (e.g., the Specification does not provide a definition that provides consistent interpretation of the term). Applicant defines “about” in [75] of the Specification: “The term "about" when used as a modifier is intended to convey that the numbers and ranges disclosed herein may be flexible as understood by ordinarily skilled artisans and that practice of the disclosed invention by ordinarily skilled artisans using properties that are outside of a literal range will achieve the desired result.” This definition of about is indefinite because it describes broad and narrow ranges and/or is indefinitely defined. “The Examiner suggests “about” should be removed and considers the claim values as if the term “about” was not present. See MPEP 2173.05(b)(i).
All claims that depend from claim 1 are additionally rejected.
Claim 4 recites “substantially” undamaged, where “substantially” is a relative term. Thus, “substantially” has not been adequately defined in the Specification [102], and the Examiner will examine the claims without the presence of the term “substantially”.
Claim 8 recites dihydroxyphenylalanine (DOPA) “derivatives” and polyethylene glycol (PEG) and its “derivatives”, in which the term “derivative” is indefinite, because it is unclear how far one can deviate from the listed parent compounds (i.e., the term “derivative” itself does not provide structure, and a PHOSITA could understand this term to mean chemical derivatization that provides compounds of different functionality) and yet still remain within the metes and bounds of the invention claimed. The Examiner will examine the scope based on the parent compound, and suggests replacement of the compound group with a specifically defined genus and/or list of intended compounds.
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.
Claims 1, 4, 6, and 9-13 are rejected under 35 U.S.C. 103 as being unpatentable over Becker (WO2015066173A1; the Examiner recognizes collaboration with Becker in the Specification, and selects the earlier published WO family member), and in further view of Zhang (CN 103948974; machine translation provided), and Policastro (Biomacromolecules, 2015).
Applicant’s claims are directed to a membrane suitable for use soft tissue repair applications comprising two or more polymer layers, wherein, generally, the fiber diameters are in the micron range, and the pore diameter is also in the micron range, and the polymer layers has a porosity of 80-95%. As a CIP, in relation to the previously examiner claims, the instant Application selects “an L-valine-co-L-phenylalanine poly(ester urea)” in instant claim 2 (i.e., compared to the previously recited “an acid-based poly(ester urea) comprising (1-PHE-6)”).
Note that the modification of the intended use (i.e., soft tissue repair of claim 1) compared to earlier applications does not provide differing patentable weight to the composition claim. Also, the electrospinning method of claim 1 suggests a product-by-process limitation, whereby the composition structure defines patentability, such that other methods of making polymer fibers are considered.
Furthermore, claims 3-4 contain potential product-by-process limitations where structural elements originating from the process will be considered in the broadest sense, but overall, the patentability of a composition depends from the structure of the composition, as plainly described by the claims: It must be remembered: "[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).
Furthermore, the functional limitation of the “membrane resorbs” in a certain amount of time of claims 9-12, does not provide structural limitations, apart from the composition is somewhat resorbable, since there is not % or amount of resorption indicated, that provides an objective amount to consider (e.g., at the end of the instant time values, there could be 100% resorption or 0.000001% resorption of the membrane). Furthermore, the Specification is not clear on what is meant by “physiological conditions” [61]. Finally, Applicant’s composition can be maintained in vivo between at least 1 month to 1 year [60], in which 1 year (365 days) exceeds the 195 day maximum of claims 9-12. Therefore, if there is resorption, there are situations where the composition is maintained beyond the instant resorption time frame. Therefore, the claims are interpreted to mean that there is “some” resorption of the membrane composition in vivo, in a broader sense.
Further note that the view of analogous reference is considered broadly: Applicant is reminded that the scope of analogous art is to be considered broadly. Wyers v. Master Lock Co., No. 2009-1412, 2010 WL 2901839 (Fed. Cir. July 22, 2010). Art is analogous if it is (1) from the same field of endeavor, regardless of the problem addressed, or (2) reasonably pertinent to the particular problem with which the inventor is involved. In re Clay, 966 F.2d 656, 658–59 (Fed. Cir. 1992). Thus, for example, applications of vascular graft tissue engineering and bone repair, both fall under the umbrella of tissue engineering generally, whereby vascular tissue is also considered a “soft” tissue.
Becker teaches films [0064], comprising amino acid-based poly(ester urea) polymers suitable for tissue repair, including vascular tissues (title, abstract) and/or produced by electrospinning, printing, etc., to produce 3D structures [0064]. Becker teaches: “As those of skill in the art will appreciate, fiber diameter, alignment, surface-to-volume ratio, and porosity can be controlled in the electrospinning process” [0065]. Furthermore, Becker teaches: “advantageously, it has been found that amino acid-based poly(ester urea)s are biodegradable, resorbable with non-toxic hydrolysis byproducts, have tunable mechanic properties, synthetic flexibility, and the ability to be synthesized so that functional groups may be included.” For example, L-leucine based PEUs are flexible, because of their bulky side chains; L-Phenylalanine based PEUs are more rigid, because of aromatic side chains (pg 24-25). Additionally, Becker teaches incorporation of the polar organic solvent of hexafluoroisopropanol (HFIP) (as discussed in instant claim 2) for processing methods such as electrospinning [0064].
Regarding claim 1: Becker further teaches L-valine copolymerized with a proteinogenic amino acid in a preferred embodiment for supporting tissue repair ([0056]; Becker – instant claim 1). Thus, a PHOSITA would use a valine-based poly(ester urea) copolymer, as a starting point for optimization, on the basis of the disclosed example that employs the electrospinning of P(1-LEU-10) (i.e., that similarly contains a bulky sidechain compared to valine to afford a flexible PEU) (pg 24-28), and further, on the basis of the permissible PEU copolymer variations taught by Becker – claims 1 and 11, in which Becker teaches that functional substitution of the copolymer allows for optimization of PEU copolymer mechanical properties for tissue repair [0064-0065]. See below:
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Furthermore, Becker teaches an electrospun film (reads on membrane) ([0064], pg 24-28), comprising copolymeric PEUs (Becker – instant claims 1 and 11) with a fiber diameter of 422 nm (converts to 0.42 um), and a pore area of 10 um2 (converts 3.6 um pore diameter, i.e., rad = 1.8 um and A=(pi)r2) [0088], in which these properties have the potential to be optimized based on electrospinning settings [0065].
Regarding claim 4: Becker teaches electrospinning generically [0064-0065] and by example (pg 24-28), including preparing a vascular graft by electrospinning onto a mandrel [0069-0075], such that the order of steps is prima facie obvious, and the patentability of a composition lies in the structure of said composition.
Regarding claim 6: Becker teaches coating different devices [0064], in which the Becker’s disclosed device is made from electrospinning [0064].
In summary, Becker teaches resorbable films comprising a valine-based poly(ester urea) copolymer, (that further incorporates a proteinogenic amino acid monomer, such as flexible or rigid amino acids, on the basis of their side chain type (pg 24-25)) (Becker – claims 1 and 11), that could be spun into a layered composition (e.g., films, coatings, etc. [0064]). However, Becker does not teach the fiber, pore diameter, porosity requirements, and explicit multi-layering of film, coating, etc. compositions (instant claim 1), the explicit teaching of resorbable days (instant claim 9-12), and antimicrobial activity (instant claim 13).
Zhang discloses a membrane formed via electrospinning used for guided tissue regeneration (see abstract, [0002-0008]) that includes a method for layer on layer electrospinning (abstract), providing single-layer or double-layer porous structures . The membrane is formed of a biolayer film of polycaprolactone or blended with degradable aliphatic polyester [0008-0009]. Zhang states the mechanical properties and degradation properties for tissue repair which membrane has good biocompatibility prevents growth of fiber cell tissue defect position. The membrane further promotes regenerative repair of tissue without further surgery [0039]. Zhang discloses the membrane can comprise two layers [0008]. Zhang discloses the membrane can comprise two layers [0008] where one layer is a dense layer having a pore diameter of 2 to 6 microns and fiber diameter of 200 nm to 1200 nm (0.2 to 1.2 microns) [0010-0011] and a second layer that is loose having a pore diameter of 5 to 100 microns and fiber diameter of 200 nm to 7 microns [0012] (i.e., reading on the pore diameter/fiber diameter embodiment of instant claim 1, by overlapping the instant property ranges). With regard to the numerical range, a prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art (see 2144.05(I)). See In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) (“A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.”). Also, Zhang teaches antibacterial material (abstract) (reads on antimicrobial activity of instant claim 13).
Policastro teaches PEU compositions for tissue repair (abstract), whereby layers of a regeneration membrane having a porosity within the range of 85-90%, that facilitates movement of materials through the scaffold construct (pg 1363; ‘Characterization of 3D porous scaffolds using Microcomputed tomography’) (reading on the porosity requirements of instant claim 1). Policastro further teaches: “in vitro degradation studies show that PEUs degrade faster than PLLA, with a 5 wt % degradation after 112 days in physiologically relevant conditions (pg 1358, ‘introduction’), which affects the resorbable property of the resulting compositions made form PEU.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the valine-based poly(ester urea) copolymer taught by Becker, with a multi-layering system that is similarly disclosed by Zhang and Policastro (i.e., multiple layer, pore diameter, fiber diameter), because Zhang states the disclosed film material has excellent mechanical properties and degradation properties for tissue repair which membrane has good biocompatibility prevents growth of fiber cell tissue defect position (abstract). The membrane further promotes regenerative repair of tissue without further surgery [0039]. Furthermore, Policastro teaches high porosity values, and their obvious use in PEU type devices. Finally, Becker teaches: “As those of skill in the art will appreciate, fiber diameter, alignment, surface-to-volume ratio, and porosity can be controlled in the electrospinning process” [0065], which is an optimization process useful for PEU compositions for tissue repair (abstract).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the valine-based poly(ester urea) copolymer taught by Becker, to add an antimicrobial component, as demonstrated by Zhang, because Zhang teaches antibacterials can suppress the incident of bacterial infection (abstract), whereby Becker’s devices are intended for invasive procedures, where sterilization is a consideration [0079].
Lastly, regarding the resorbable property (instant claims 9-12): Policastro further teaches: “in vitro degradation studies show that PEUs degrade faster than PLLA, with a 5 wt % degradation after 112 days in physiologically relevant conditions (pg 1358, ‘introduction’), which affects the resorbable property of the resulting compositions made form PEU. This is echoed by Becker who teaches the same PEUs as resorbable, in which the biodegradability can be tuned by the variability of copolymer structure (Becker - claim 11, [0004]). Thus, the resorption property is a result-effective variable which a PHOSITA could optimize by modifying the chemical structure of the polymer and the resulting membrane device. See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (indicating 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). Furthermore, when the combined Prior Art teaches similar film compositions, using the same copolymer, then the resorption time for that film composition is expected to be similar to the instantly recited time periods provided in the instant claims.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over Becker (WO2015066173A1), Zhang (CN 103948974; machine translation provided), and Policastro (Biomacromolecules, 2015), as applied to claims 1, 4, 6, and 9-13 above, and in further view of Gao (ACS Biomater. Sci. Eng., 2015), Stamberg (US20140163601), Vasita (Polymer, 2010), Milella (J Biomed Mater Res. 2001), Hunter (US20050142163), Goonoo (European Journal of Pharmaceutics and Biopharmaceutics, 2015), and Pham (Biomacromolecules, 2006).
As discussed above, the combined Prior Art teaches the obviousness of the multilayer composition of instant claim 1, comprising valine-based poly(ester urea) copolymers (i.e., that further incorporates a proteinogenic amino acid monomer, such as flexible or rigid amino acids, on the basis of their side chain type (pg 24-25)) (Becker – claims 1 and 11), and further limitations of some dependent claims. However, they do not teach the explicit selection of the phenylalanine-based subunit of the copolymer within the narrowed “an L-valine-co-L-phenylalanine poly(ester urea)” (instant claim 2), “mechanical integration and binding between the layers is enhanced by electrospinning wet fibers by decreasing the screen distance before electrospinning the subsequent layer” (instant claim 3), to the membrane has a non-ionic surfactant (instant claims 5), coating the membrane (instant claims 7-8), polydioxanone in the membrane (instant claims 14-16), and a third layer (instant claims 17-20).
Gao teaches leucine based PEUs for vascular tissue engineering. Notably, Gao teaches that L-phenylalanine-based PEU (poly(1-PHE-6)) was shown to be resorbable and nontoxic in subcutaneous rat implant models (regarding instant claim 2) (pg 795, col 2). Furthermore, Gao teaches that that the physical, chemical, and degradation properties of PEU polymers are influenced by specific α-amino acids and diol lengths in the monomers (i.e., increasing chain diol length in the monomer increases the amount of flexible segment in the polymer structures, which results in reduced elastic modulus values and increased elongation at break), and that PEUs advantageously degrade in vivo faster than other commonly used polymers in tissue engineering devices, such as PCL (pg 795).
Stamberg discloses electrospun medical devices (abstract), whereby maximizing fiber bonding and minimizing delamination between layers in an electrospun membrane by lowering the fabrication distance to cause bonding of fibers between layers resulting in wetter fibers and tighter bonds (regarding instant claim 3) (see 0051).
Vasita discloses poly(lactide co-glycolide) membranes used in tissue engineering and making the surface of the membranes more hydrophilic by blending with a non-ionic surfactant such as Pluronic F-108 (regarding instant claim 5)(see abstract). Vasita states adding small amounts of the surfactant allows the surfactant to segregate to the surface of the membrane changing the surface wettability while maintaining the bulk mechanical properties (see section 1. Introduction). The improved surface hydrophilicity improves cell adherence and growth (see section 1. Introduction).
Milella discloses a poly(l-lactide) acid membrane for guided tissue regeneration to treat bone defects that have good biocompatibility (Figure 1, pg 249). Milella discloses providing the membrane with an alginate film (i.e., a film coating) acting as a vehicle for growth factors to promote osteogenesis (regarding instant claims 7-8) (see abstract).
Hunter discloses membranes for guided tissue regeneration membranes (see 0036, 0457). Hunter further teaches the use of polymer such as polydioxanone and poly (ester urea), or copolymers there of as biodegradable polymers for such devices (regarding instant claims 14-16) (see 0131).
Goonoo discloses polydioxanone in membranes for tissue regeneration (regarding instant claims 14-16). Goonoo teaches polydioxanone offers a softness and flexibility to the membranes and can be used as a copolymer in such membranes (See abstract, section 3.3).
Pham discloses an electrospun membrane that is formed of multiple layers (regarding instant claims 17-20). The layers alternate between nano and microfibers which provides the scaffold with properties of both nanofibers and microfibers which can influence the behavior of the cell such as migration and spreading (see Introduction, Results and Conclusion).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to modify the valine-based poly(ester urea) copolymer taught by Becker, with an additional L-phenylalanine-based PEU segment taught by Gao, because L-phenylalanine-based PEU segments are nontoxic, efficacious in tissue treatment, and the physical, chemical, and degradation properties of PEU polymers are influenced by specific α-amino acids and diol lengths in the monomers (i.e., increasing chain diol length in the monomer increases the amount of flexible segment in the polymer structures, which results in reduced elastic modulus values and increased elongation at break) (pg 795), as taught by Gao. Furthermore, Becker teaches that L-Phenylalanine-based PEU segments provide rigidity to a PEU polymer on the basis of their aromatic side chains, in order to provide optimization of mechanical properties (pg 24-25), while Becker provides a copolymer starting point already comprising a valine-based poly(ester urea) copolymer (i.e., that further incorporates a proteinogenic amino acid monomer, such as flexible or rigid amino acids, on the basis of their side chain type (pg 24-25)) (Becker – claims 1 and 11).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify membrane of the combined Prior Art to include moving the distance during the electrospinning process as taught by Stamberg. One would have been motivated to do so since both are directed to forming implantable multiple layer membranes using electrospinning while Stamberg further teaches by decreasing the distance between the layers, the binding is enhanced and delamination is minimized (thereby, reading on instant claim 3).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the membrane of combined Prior Art to include treatment with the non-ionic surfactant during formation of the membrane as taught by Vasita. One would have been motivated to do so since both are directed to the use of hydrophobic polymers for forming membranes for tissue engineering where Vasita states including the surfactant provides improved surface wetting properties, which is desired on the surface of the membranes to improve cell adherence and growth (thereby, reading on instant claim 5).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the membrane of combined Prior Art to include coating the membrane with alginate as taught by Milella. One would have been motivated to do so since both are directed to tissue or bone regeneration membranes formed of polymers where Milella further teaches treating with alginate in order to promote osteogenesis which is desired in tissue regeneration barrier membrane (thereby, reading on instant claims 7-8).
It would have been obvious to one having ordinary skill in the art before the effective date of the claimed invention to modify the membrane of combined Prior Art to include polydioxanone as shown by Hunter and Goonoo. One would have been motivated to do so since both are directed to forming membranes for tissue regeneration where Hunter shows that polydioxanone can be used with polyester urea to form such membranes and Goonoo further teaches that polydioxanone can provide a softness and flexibility to the membrane which is desired when used for tissue regeneration within the body (thereby, reading on instant claims 14-16).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the membrane combined Prior Art to include a third layer in order to optimize the membrane cell activity as taught by Pham. One would have been motivated to do so since both are directed to multilayered membranes having different sized fibers where Pham further teaches alternating the layers can allow for the membrane to have both the benefits from micro and nanofibers and can control the cell properties (thereby, reading on instant claims 17-20).
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RAJAN PRAGANI whose telephone number is (703)756-5319. The examiner can normally be reached 7a-5p EST (M-Th).
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/R.P./Examiner, Art Unit 1614 9/3/2026
/SEAN M BASQUILL/Primary Examiner, Art Unit 1614
