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 .
Claim Objections
Claim 1 is objected to because of the following informalities: The claim recites the acronym EDTA. The full name should appear in the claims before the first use of an acronym. Appropriate 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 1-12 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.
The phrase “tightly closed” in claim 1 is a relative phrase which renders the claim indefinite. The term “tightly” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 1 recite concentrations in percentages of the sodium dodecyl sulfate solution that is also recited. The basis of the percentage (e.g., mass/weight, volume, molar, etc.) is note detailed. Thus the scope if the claim is unclear.
Claim 6 recites the limitation "the sterile physiological saline" in lines 3-4. There is insufficient antecedent basis for this limitation in the claim because sterility was not mentioned in the parent claim.
Claims that are rejected, but are not explicitly elaborated upon, are also indefinite because they depend from an indefinite claim and do not add clarity.
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, 6, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Sulner et al. (US PGPub No. 2007/0038298) in view of Matheny et al. (US PGPub No. 2012/0302499 – see IDS), Song et al. (US PGPub No. 2008/0147019 – see IDS), Ward et al. (US PGPub No. 2010/0028396), Murray et al. (US PGPub No. 2015/0367030), Min et al. (US PGPub No. 2010/0137203), Mitchell et al. (US PGPub No. 2002/0115208), Christ et al. (WO 2012/021814), Depaula et al. (US PGPub No. 2011/0070284), Boccaccini et al. (Journal of the Ceramic Society of Japan 2006:114(1)1-14), Chudinova et al. (Materials Science and Engineering 2016 116(012004):1-6), and Lopez et al. (Applied Surface Science 2013 280:715-719).
Sulner et al. teach a collagen biofabric composed of decellularized amniotic membrane (fetal amniotic membrane) (see abstract and paragraph 29; instant claim 1). The tissue is subjected to serological testing, decellularized, dehydrated, and sterilized (see paragraphs 218, 221, 226-228, and 229-230; instant claims 1 and 12). The biofabric may also be impregnated with therapeutic agents, such as anti-infectives where silver is envisioned (see paragraphs 22 and 40). Sulner et al. discuss decellularization with a detergent solution, where sodium dodecyl sulfate (SDS) is a preferred option and they also envision decellularization treatment with an enzyme solution such as trypsin solution (see paragraph 218). When incubated in the solution, the membrane is completely covered (dipped) in a closed container (see paragraph 310). They highly prefer the addition of chelating agents, such as ethylenediaminetetraacetic acid (EDTA), in the treatment, washing, and storage solutions to discourage protease activity as well as a hypotonic aqueous solutions for cell lysis (see paragraph 219). They detail washing the membrane to remove cellular debris in a physiological saline after treatment in decellularization solution to remove cellular debris as well as agitation on a moving platform for solution treatment and washing steps (see paragraphs 223 and 309-317). Sulner et al. also teach repeating the decellularization steps as necessary to achieve the desired degree of decellularization (see paragraph 223). Incubation times in the solutions range from 15-120 minutes (see paragraph 223). Further, sterilization via techniques such as irradiation are envisioned (see paragraph 239; instant claim 1). The specific timing and concentrations in the solution treatment regimen, as instantly claimed, and electrophoretic loading of the anti-infective are not detailed.
Matheny et al. teach an extracellular matrix (ECM) that is obtained from tissue (see abstract). Here placental tissue is contemplated and the process of preparation results in a decellularized and sterilized matrix (see paragraph 35). Matheny et al. go on to teach the incorporation of additives into the ECM during wet processing, where copper nanoparticles, silver nanoparticles, and gold nanoparticles are explicitly named amongst the envisioned materials (see paragraph 69; instant claim 5).
Song et al. detail that uniform distribution of silver nanoparticles in a matrix is important for overall efficacy against bacteria (see paragraph 23). They additionally teach the efficacy of copper nanoparticles in a matrix as an antibacterial active (see paragraph 48).
Ward et al. teach SDS solutions employed in the decellularization of tissue and detail several viable concentrations including 0.01% (see paragraphs 4, 19, and 125). They also teach repeated washing steps, where the duration of each step is 15 minutes (see paragraph 134).
Murray et al. also teach tissue decellularization via solution treatments with SDS and trypsin, where the duration of solution exposure and temperature can be selected as desired and is envisioned as 1 hour and room temperature, respectively (see paragraphs 43 and 47).
Mitchell et al. teach tissue decellularization due to treatment with a series of solutions, where an SDS solution is applied at room temperature for one hour (see abstract and paragraph 146). The also detail three washes in a physiological saline after the decellularization solution treatment (see paragraph 158).
Min et al. teach decellularization of a tissue prepared in vitro (see abstract). Here, an SDS solution treatment was followed by a trypsin-EDTA solution treatment which was followed by five washes in physiological saline (see paragraph 68).
Christ et al. teach decellularizing tissue with a series of solutions, where a solution of trypsin and EDTA is applied for 1 hour at 37⁰C as part of the process (see page 3 second full paragraph and page 18 second full paragraph).
Depaula et al. teach agitated incubation of a decellularized membrane in a treatment solution on an orbital shaker in a container with a lid to avoid splashing liquid (see paragraphs 234-237).
Boccaccini et al. teach the benefit of electrophoretic deposition for loading inorganic/metallic nanoparticles into porous structures (see page 5-page 7 second column third full paragraph). They detail that the process promotes the infiltration of the nanoparticles into fibrous mats, even when the mat is not conductive (see page 5 second column last full paragraph). Boccaccini et al. also discuss the deposition of silver nanoparticles (see page 7 second column first full paragraph).
Chudinova et al. teach the electrophoretic deposition of silver nanoparticles from a dispersion/suspension onto a porous/textured surface placed in (see abstract and page 2 third full paragraph and figure 1). They teach an applied voltage of 50V for 30 minutes (see page 2 third full paragraph).
Lopez et al. teach electrophoretic deposition of silver nanoparticles from an aqueous suspension liquid (see page 716 first column second-third full paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and evenly distribute silver nanoparticles as an anti-infective drug in the membrane of Sulner et al. This choice would have been obvious in light of their contemplation of silver as an anti-infective additive as well as Matheny et al. who suggest their inclusion in a decellularized tissue. The selection also is obvious as the simple substitution of one known element for another in order to yield a predictable outcome (e.g., specific anti-infective for generic anti-infective). Uniform distribution of the nanoparticles in the matrix, as taught by Song et al., also would have been obvious as the application of the same technique to yield the same improvement (e.g., antibacterial efficacy). Prior art, including Min et al., Murray et al. Christ et al., Mitchell et al., and Ward et al. recognized the utility of trypsin in the presence of EDTA as well as SDS as known decellularizing solutions that can be employed alone or in sequence for various times and at various concentrations and temperatures. Since Sulner et al. teach 1) conducting detergent and enzyme based decellularization of the amniotic tissue as desired with repetition of their applications and 2) following the decellularization treatment with rinsing in physiological saline, as the other noted references discuss in more detail, it would have been obvious to select amongst the known options for decellularization solution treatment steps. Specifically, it would have been obvious to employ a repeated sequence of solution treatments of 0.01% SDS for 1 hour at room temperature followed by trypsin-EDTA for one hour at 37⁰C. The repetition is obvious in light of the suggestion of Sulner et al. and yields a series of treatments in SDS, trypsin-ETDA, and SDS, as instantly claimed. The presence of a pH marker is not detailed in the trypsin solutions and therefore is interpreted as absent. Multiple rinses after the application of a decellularization solution is detailed repeatedly across the cited prior art, thus the inclusion of three or five 15 minute rinses after each or both chemical treatments would have been obvious so as to remove cellular debris as a result of the chemical treatment. Agitation on a moving platform where an orbital shaker is employed along with a closed container for the membrane to thwart solution splashing during solution treatments and rinses would have been obvious in light of Depaula et al. and Sulner et al. The orbital shaker is an alternative means to agitate the membrane during the decellularization process (simple substitution of one known method for another in order to yield a predictable outcome). Regarding the even loading of silver nanoparticles, Boccaccini et al. motivate the use of electrophoretic deposition for this process due to its utility to load inorganic nanoparticles that penetrate into the depth of desired matrices and its suitability for loading such a nanoparticles within a fabric. It would then follow to employ known loading conditions for silver nanoparticles including the dispersion medium (aqueous) for the silver as well as electrophoretic treatment conditions of 50 volts for 30 minutes as detailed by Chudinova et al. and Lopez et al. Dehydration followed by sterilization via irradiation to produce a dried finished product as detailed by Sulner et al. would then follow. The loading of copper nanoparticles instead of silver nanoparticles would also have been obvious because they are also contemplated for their anti-infective properties by Song et al. and incorporation into decellularized placenta is envisioned by Matheny et al. Therefore claims 1, 6, and 12 are obvious over Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., and Lopez et al.
Claims 1-2, 6, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., and Lopez et al. as applied to claims 1, 6, and 12 above, and further in view of Wang et al. (US PGPub No. 2009/0142836) and the University of Delaware Biosafety Manual (2015).
Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., and Lopez et al. render obvious the limitations of instant claims 1, 6, and 12. They do not detail performing the dehydration step in a cabinet as detailed by the instant claims.
Wang et al. teach drying/dehydrating a decellularized sterile tissue matrix in the airflow of a sterile laminar hood (see abstract and paragraphs 85-86). They note a higher final water content when air dried as opposed to vacuum drying and that the two methods are alternatives (see paragraph 85). The University of Delaware Biosafety Manual details that sterile laminar hoods are biosafety cabinets equipped with a HEPA filter that removes over 99.5% of particles (see page 6-1).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the drying/dehydrating steps in the modified method of Sulner et al. in a sterile laminar hood as detailed by Wang et al. because they teach it as a known option and alternative for drying a similar matrix. This modification would have been obvious as the simple substitution of one known technique for another in order to yield predictable outcome. Therefore claims 1-2, 6, and 12 are obvious over Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., Lopez et al., Wang et al., and University of Delaware Biosafety Manual.
Claims 1, 3, 6, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., and Lopez et al. as applied to claims 1, 6, and 12 above, and further in view of Dashti et al. (US PGPub No. 2018/0272037).
Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., and Lopez et al. render obvious the limitations of instant claims 1, 6, and 12. They detail sterilization of the membrane, but do not explicitly detail UV irradiation for a particular time period to achieve this end.
Dashti et al. teach sterilizing a decellularized membrane via UV irradiation (see paragraph 20, 44 and 61). Here they sterilize decellularized matrices with irradiation with UV light for 30 minutes (see paragraph 61).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the sterilization in the modified method of Sulner et al. via UV irradiation for 30 minutes as detailed by Dashti et al. because they demonstrate its utility for sterilizing a similar matrix. This modification would have been obvious as the simple substitution of one known technique for another in order to yield predictable outcome. Therefore claims 1, 3, 6, and 12 are obvious over Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., Lopez et al., and Dashti et al.
Claims 1-4, 6, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., Lopez et al., Wang et al., and University of Delaware Biosafety Manual as applied to claims 1-2, 6, and 12 above, and further in view of Dashti et al.
Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., Lopez et al., Wang et al., and University of Delaware Biosafety Manual render obvious the limitations of instant claims 1-2, 6, and 12. They detail sterilization of the membrane, but do not explicitly detail UV irradiation for a particular time period to achieve this end.
Dashti et al. teach sterilizing a decellularized membrane via UV irradiation (see paragraph 20, 44 and 61). Here they sterilize decellularized matrices with irradiation with UV light for 30 minutes (see paragraph 61).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the sterilization in the modified method of Sulner et al. via UV irradiation for 30 minutes as detailed by Dashti et al. because they demonstrate its utility for sterilizing a similar matrix. This modification would have been obvious as the simple substitution of one known technique for another in order to yield predictable outcome. Therefore claims 1-4, 6, and 12 are obvious over Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., Lopez et al., Wang et al., University of Delaware Biosafety Manual, and Dashti et al.
Claims 1, 6-7, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., and Lopez et al. as applied to claims 1, 6, and 12 above, and further in view of Kruk et al. (Kruk et al. (Colloids and Surfaces B: Biointerfaces 2015 128:17-22 – see IDS) and Karandikar et al. (US PGPub No. 2007/0003603 – see IDS).
Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., and Lopez et al. render obvious the limitations of instant claims 1, 6, and 12. The size of the nanoparticles for anti-infective use is not detailed nor is the combination of copper and silver nanoparticles exemplified.
Kruk et al. teach the utility of metal nanoparticles with bacteriocidal activity in polymers as composite materials to exploit the properties of the nanoparticles (see page 18 first column first partial paragraph). Copper nanoparticles are further taught as a particular variety of antimicrobial nanoparticle to employ (see page 18 first column first full paragraph). The nanoparticles had an average size of 50 nm and a distribution between 25 and 110 nm, where the majority fall between 25 and 60 nm (see figure 2 and page 19 second column last partial paragraph). The copper nanoparticles were effective against several strains of gram positive bacteria and some antibiotic resistant bacterial stains as well (see tables 1-2 and page 21 second column last partial paragraph).
Karandikar et al. teach silver nanoparticles that are envisioned for inclusion in collagen matrices to confer antimicrobial properties (see abstract and paragraphs 9 and 12). The silver nanoparticles have a size of 0.1 to 100 nm (see paragraph 9).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select the nanoparticles of Kruk et al. as an anti-infective copper nanoparticles and the silver nanoparticles of Karandikar et al. for this same purpose. The combination is obvious because both are known metallic anti-infective agents and the combination of two components known for the same purpose is obvious. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (see MPEP 2144.06). The selection of these particular nanoparticles also is obvious as the simple substitution of one known element for another in order to yield a predicable outcome (e.g. specific nanoparticles vs generic nanoparticles). Therefore claims 1, 6-7, and 12 are obvious over Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., Lopez et al., Kruk et al. and Karandikar et al.
Claims 1, 6-7, 10, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., Lopez et al., Kruk et al. and Karandikar et al. as applied to claims 1, 6-7, and 12 above, and further in view of Ahmad et al. (Colloids and Surfaces B: Biointerfaces 2013 107:227-234 – see IDS).
Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., Lopez et al., Kruk et al. and Karandikar et al. render obvious the limitations of instant claims 1, 6-7, and 12. The presence of gold nanoparticles as anti-infective agents is not detailed.
Ahmad et al. teach the efficacy of monodisperse silver nanoparticles and monodisperse gold nanoparticles as antimicrobial actives (see abstract and page 232 first column second paragraph). The gold nanoparticles have an average size of 5 nm and the silver nanoparticles have an average size of 30 nm (see table 1). Both were effective against gram positive and gram negative bacteria (see page 232 first column second paragraph).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to add the nanoparticles of Ahmad et al. as anti-infective agents along with the silver and copper nanoparticles in the modified collagen matrix made by Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., Lopez et al., Kruk et al. and Karandikar et al. This modification would have been obvious because Matheny et al. list each of them for inclusion in such decellularized tissues and Karandikar et al. explicitly envisioned anti-infective metal nanoparticles in collagen matrices. The modification also would have been obvious as the simple substitution of one known element for another in order to yield a predictable outcome. The modification combines multiple known anti-infective metal nanoparticles. “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (see MPEP 2144.06). Therefore claims 1, 6-7, 10, and 12 are obvious over Sulner et al. in view of Matheny et al., Song et al., Ward et al., Murray et al., Min et al., Mitchell et al., Christ et al., Depaula et al., Boccaccini et al., Chudinova et al., Lopez et al., Kruk et al., Karandikar et al., and Ahmad et al.
Relevant Prior Art
Quantum dots as anti-infective additives were known in the art. Neelgund et al. (Colloids and Surfaces B: Biointerfaces 2012 100:215-225 – see IDS) teach carbon nanotubes that are surface functionalized with a dendrimer within which cadmium selenium quantum dots are entrapped (mixture with cadmium quantum dots) (see abstract and scheme 1). This combination with dendrimers is taught to reduce the cellular toxicity of the quantum dots (see page 216 first column first full paragraph). The quantum dots themselves and when included on the dendrimer coated surface are shown to have antimicrobial properties against both gram negative and gram positive bacteria (see figure 6). The quantum dot containing carbon nanotubes are taught for inclusion in medicine and materials in order to confer antimicrobial properties (see page 220 second column last paragraph-page 221 first column first partial paragraph). Quantum dots were also known to be deposited by electrophoretic deposition; however, when disclosed, the deposition suspension concentration does not appear to suggest the instantly claimed concentration (see Krishnamurthy et al. ChemPhysChem 2014 15: 2129–2135, abstract and page 2134 second column second full paragraph).
Deposition of silver nanoparticles via electrophoretic deposition was known in the art as discussed in the prior art rejections above. However, when disclosed, the deposition suspension concentration does not appear to suggest the instantly claimed concentration (see Bartmanski et al. Ceramics International 2017 43:11820-11829, page 11821 second column fourth full paragraph).
Conclusion
No claim is allowed.
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/CARALYNNE E HELM/ Examiner, Art Unit 1615
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