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 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.
Claims 1-2, 5-6, 11, 13-14, and 17-19 are rejected under 35 U.S.C. 103 as being unpatentable
over Kim et al. US Pub.: US 20210108180 A1, hereinafter Kim.
Regarding claim 1, Kim teaches a 3-dimensional (3D) electrogel scaffold comprising piezoelectric
nanoparticles uniformly dispersed throughout a homogenous hydrogel polymer matrix (paragraph 33, 37 and 114); The hybrid hydrogels of the disclosure comprise one or more biocompatible electroconductive nanomaterials, such as nanoparticles. The one or more biocompatible conductive nanomaterials is homogenously dispersed within the hydrogel. These new materials allow engineering 3D human tissues.
wherein the hydrogel polymer matrix is gelled (paragraph 33, 37 and 114). Hydrogels could be further increased with the addition of transglutaminase, thereby providing yet another degree of tunability to the hybrid material.
However, Kim does not explicitly teach wherein the hydrogel polymer matrix comprises crosslinked alginate, carboxymethyl-chitosan and agarose polymers.
Ryan teaches a system for sealing a channel in tissue and further explicitly teaches a crosslinking hydrogel polymer matrix (paragraph 182-183). Hydrogels may be crosslinked to provide improved properties, for example to increase the residence time of the hydrogel in vivo.
Therefore it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the polymer matrix from Kim with the crosslinking matrix from Ryan for the benefit of increasing the residence time of the hydrogel in vivo
Mao teaches in vivo synthesis of connective tissues and further teaches wherein the hydrogel polymer matrix comprises alginate, carboxymethyl-chitosan and agarose polymers (paragraph 26 and 38). The scaffold of the composition is a natural material selected from the group consisting of alginate, chitosan, and agarose.
Therefore it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the combination of polymers in the matrix from Kim with the composition from Mao for the benefit of increasing biocompatibility and to aid in the regeneration of new tissue.
Regarding claim 2, Kim in view of Ryan in view of Mao teaches the claimed invention and Kim
further teaches wherein the homogenous hydrogel polymer matrix is a porous hydrogel polymer matrix (paragraph 19 and 94). The hydrogels possessed a porous network similar to that of decellularized native porcine myocardium.
Regarding claim 5, Kim in view of Ryan in view of Mao teaches the claimed invention and Mao
further teaches wherein the piezoelectric nanoparticles are dispersed within the matrix with the aid of a polymer coating around the nanoparticles that includes one or more of agarose, poly-D-lysine, poly-D-ornithine, gum Arabic (paragraph 26 and 38). The scaffold of the composition is a natural material selected from the group consisting of agarose. This may be coated on the nanoparticles from Ryan.
Regarding claim 6, Kim in view of Ryan in view of Mao teaches the claimed invention and Kim
further teaches wherein the porous structure has a spongy or trabecular porous structure (paragraph 19 and 94). The hydrogels possessed a porous network similar to that of decellularized native porcine myocardium. Porous hydrogels are spongy in nature.
Regarding claim 11, Kim in view of Ryan in view of Mao teaches the claimed invention and Kim
further teaches a uniform dispersion of cells throughout the porous hydrogel polymer matrix (paragraph 33, 37 and 114); The hybrid hydrogels of the disclosure comprise one or more biocompatible electroconductive nanomaterials, such as nanoparticles. The one or more biocompatible conductive nanomaterials is homogenously dispersed within the hydrogel
Regarding claim 13, Kim in view of Ryan in view of Mao teaches the claimed invention and Kim
further teaches wherein the cells are one or more types of stem cells (paragraph 44). The cells may be stem cells. Suitable stem cells include human adipose-derived stem cells (hADSCs).
Regarding claim 14, Kim in view of Ryan in view of Mao does not teach wherein the hydrogel
matrix comprises alginate, carboxymethyl-chitosan and agarose polymers in a ratio of 0.5- 5%:5%:1 .5% (w/v).
However, Mao teaches wherein the hydrogel matrix comprises alginate, carboxymethyl-chitosan and agarose polymers (paragraph 26 and 38). Accordingly, Mao teaches that the combination ratio of alginate, carboxymethyl-chitosan and agarose polymers is a result-effective variable which achieves a balance of mechanical strength, biocompatibility, and tunable swelling, and discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233 (See MPEP §2144.05). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the ratio of polymers in order provide a biocompatible scaffold to be implanted into a host.
Regarding claim 17, Kim in view of Ryan in view of Mao teaches the claimed invention and Kim
further teaches wherein the piezoelectric nanoparticles are present at a concentration of up to 7.5 mg/ml, preferably of up to 5 mg/ml (paragraph 61). Dry weights of lyophilized decellularized extracellular matrices (dECM) were determined and the samples were digested at a concentration of 5 mg/mL.
Regarding claim 18, Kim in view of Ryan in view of Mao teaches the claimed invention and Kim
further teaches wherein the hydrogel is electronically conductive (paragraph 37). The hydrogels comprise gold nanoparticles, which are highly electronically conductive.
Regarding claim 19, Kim in view of Ryan in view of Mao teaches the claimed invention and Kim
further teaches wherein the piezoelectric nanoparticles are in the form of nanospheres, nanofibers, nanotubes, nanocubes, or combinations thereof (paragraph 37). Any suitable biocompatible conductive nanomaterial can be used in the hydrogels of the disclosure, such as carbon nanotubes, graphene derivatives, gold nanoparticles, gold nanowires, choline chloride, or combinations thereof.
Regarding claim 50, Kim in view of Ryan in view of Mao teaches the claimed invention and Kim
further teaches a 3D scaffold in the form an engineered scaffold or tissue which is functional human tissue, including neural, bone or cardiac functional tissue (paragraph 99). Collagen I hydrogel was selected as a control scaffold material that was closest in approximation to the biochemical make-up of dECM and is commonly used to fabricate 3D cardiac tissues.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Kim in view of Ryan
in view of Mao in view of SHEFI et al. US Pub.: US 20190046692 A1, hereinafter Shefi.
Regarding claim 3, Kim in view of Ryan in view of Mao does not teach wherein individual
piezoelectric nanoparticles or agglomerates of nanoparticles are uncoated that is they are free of a distinct layer or coating of dispersant and/or cationic polymer.
Shefi teaches a system for guiding growth of cell components and further teaches wherein
individual piezoelectric nanoparticles or agglomerates of nanoparticles are uncoated that is they are free of a distinct layer or coating of dispersant and/or cationic polymer (paragraph 544-545). Uncoated iron oxide nanoparticles.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the nanoparticles of Kim in view of Ryan in view of Mao to be uncoated from Shefi for the benefit of optimizing fiber alignment.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Kim in view of Ryan in view
of Mao in view of Ryan in view of Mao in view of Fan et al. US Pub.: US 20200171208 A1, hereinafter Fan.
Regarding claim 8, Kim in view of Ryan in view of Mao teaches a porous hydrogel polymer
Matrix (paragraph 19 and 94). The hydrogels possessed a porous network similar to that of decellularized native porcine myocardium.
However, Kim in view of Ryan in view of Mao does not teach wherein a porous structure has a
combination of large and small pores sized from 25-50 pm and 10-20 pm respectively.
However, Fan teaches that the 3D scaffolds with mainly wall-like porous scaffolds are currently the most investigated to date. In spite of the adjustable pore size, the low interconnectivity of pores in the scaffolds limit infiltration, migration and growth of cells and tissues as well as the transport of oxygen, nutrients and wastes (paragraph 191-192). Accordingly, Fan teaches that the pore size diameter of 50-1000 nm is a result-effective variable and discovering the optimum or workable ranges involves only routine skill in the art. In re Aller, 105 USPQ 233 (See MPEP §2144.05). Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to optimize the large and small pore sizes in order provide the migration and growth of cells and tissues as well as the transport of oxygen, nutrients and wastes.
Claim 9-10 is rejected under 35 U.S.C. 103 as being unpatentable over Kim in view of Ryan in
view of Mao in view of Ryan in view of Mao in view of SHEA et al. US Pub.: US 20190008971 A1, hereinafter Shea.
Regarding claim 9, Kim in view of Ryan in view of Mao does not teach wherein the average
diameter of individual nanoparticles in the electrogel is 500 nm or less.
Shea teaches an implantable scaffold for cancer cells and further teaches wherein the average
diameter of individual nanoparticles in the electrogel is 500 nm or less (paragraph 73). The largest cross-sectional diameters of a particle within a scaffold is less than about 500 nm, 400 nm, 300 nm, 200 nm or 100 nm.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the average diameter of nanoparticles from Kim in view of Ryan in view of Mao with the diameter from Shea for the benefit of allowing the nanoparticles to interact more effectively with cells at the nanoscale, promoting cell adhesion, proliferation, and differentiation (paragraph 41, 49, and 75).
Regarding claim 10, Kim in view of Ryan in view of Mao does not teach wherein the average
diameter of nanoparticle agglomerations in the matrix is from 400 nm to 200 pm, preferably <1500 nm.
Shea teaches an implantable scaffold for cancer cells and further teaches wherein the average
diameter of nanoparticle agglomerations in the matrix is from 400 nm to 200 pm, preferably <1500 nm.
(paragraph 73). The largest cross-sectional diameters of a particle within a scaffold is less than about 500 nm, 400 nm, 300 nm, 200 nm or 100 nm.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the average diameter of nanoparticles from Kim in view of Ryan in view of Mao with the diameter from Shea for the benefit of allowing the nanoparticles to interact more effectively with cells at the nanoscale, promoting cell adhesion, proliferation, and differentiation (paragraph 41, 49, and 75).
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over Kim in view of Ryan in
view of Mao in view of Ryan in view of Mao in view of Hasselmann et al. US Pub.: US 20210340492 A1, hereinafter Hasselmann.
Regarding claim 20, Kim in view of Ryan in view of Mao does not teach wherein the
piezoelectric nanoparticles are selected from the group consisting of: barium titanate nanoparticles (BTNPs), boron-nitride nanoparticles, poly(vinylidene fluoride) (PVDF) nanoparticles and combinations thereof.
Hasselmann teaches a structured composite matrix nanoparticle material and further teaches the nanoparticles consist of magnetic, piezoelectric or other magnetic/electroactive materials such a barium titanate (BTNPs) or polyvinylidene fluoride (paragraph 164 and 180).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the nanoparticles of Kim in view of Ryan in view of Mao to add materials from Hasselmann for the benefit of allowing moving structuresto be generated using external magnetic fields, or the magnetite particles can be used as contrast agents for MRI or MPI to monitor the structures (paragraph 164).
Claims 56-57 and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Kim in view
of Ryan in view of Mao in view of Ryan in view of Mao in view of PATEN et al. US Pub.: US 20170360986 A1, hereinafter Paten.
Regarding claim 56, Kim in view of Ryan in view of Mao does not teach a 3D scaffold in the form
of an electric nerve guide comprising a support and the 3D electrogel scaffold disposed on an inner surface of said support, wherein the inner surface of the support encases injured nerves
Paten teaches a collagenous tissue repair device and further teaches a 3D scaffold in the
form of an electric nerve guide comprising a support and the 3D electrogel scaffold disposed on an inner surface of said support, wherein the inner surface of the support encases injured nerves (paragraph 58). The sheath allows the molecules of the tissue remodeling solution to remain in concentrated form near the remodeling site, and to create a local environment or milieu which is suitable for remodeling. The sheath can be a membrane or sack that is permeable or selectively permeable, and is preferably fabricated of a biodegradable polymer or a protein or other biopolymer such as collagen.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the outside of the 3D electogel scaffold with the membrane from Paten for the benefit of allowing the molecules of the tissue remodeling solution to remain in concentrated form near the remodeling site, and to create a local environment or milieu which is suitable for remodeling.
Regarding claim 57, Kim in view of Ryan in view of Mao does not teach wherein the support is a
semi-permeable support for diffusion of nutrients whist acting as a barrier to scar-forming cells or wherein the support is a membrane comprising a polymer membrane.
Paten teaches a collagenous tissue repair device and further teaches wherein the support is a semi-permeable support for diffusion of nutrients whist acting as a barrier to scar-forming cells or wherein the support is a membrane comprising a polymer membrane (paragraph 58). The sheath allows the molecules of the tissue remodeling solution to remain in concentrated form near the remodeling site, and to create a local environment or milieu which is suitable for remodeling. The sheath can be a membrane or sack that is permeable or selectively permeable, and is preferably fabricated of a biodegradable polymer or a protein or other biopolymer such as collagen.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the outside of the 3D electogel scaffold with the membrane from Paten for the benefit of allowing the molecules of the tissue remodeling solution to remain in concentrated form near the remodeling site, and to create a local environment or milieu which is suitable for remodeling.
Regarding claim 59, Kim in view of Ryan in view of Mao does not teach wherein the membrane
is an electrocompacted collagen membrane.
Paten teaches a collagenous tissue repair device and further teaches wherein the membrane
is an electrocompacted collagen membrane (paragraph 58). The sheath allows the molecules of the tissue remodeling solution to remain in concentrated form near the remodeling site, and to create a local environment or milieu which is suitable for remodeling. The sheath can be a membrane or sack that is permeable or selectively permeable, and is preferably fabricated of a biodegradable polymer or a protein or other biopolymer such as collagen.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the outside of the 3D electogel scaffold with the membrane from Paten for the benefit of allowing the molecules of the tissue remodeling solution to remain in concentrated form near the remodeling site, and to create a local environment or milieu which is suitable for remodeling.
Claim 63 is rejected under 35 U.S.C. 103 as being unpatentable over Kim in view of Ryan in
view of Mao in view of Ryan in view of Mao in view of Nguyen et al. US Pub.: US 20200276018 A1, hereinafter Nguyen.
Regarding claim 63, Kim in view of Ryan in view of Mao teaches the claimed invention and Kim
further teaches method of repair and/or regeneration of tissue malfunction or injury comprising the steps of: providing the 3D electrogel scaffold of claim 1, as an implant (paragraph 99); Three-dimensional engineered heart tissues (EHTs) were generated and is commonly used to fabricate 3D cardiac tissues.
positioning the implant at the site of the malfunctioned tissue or injured tissue (paragraph 99); The injured site would be the heart.
However, Kim in view of Ryan in view of Mao does not teach electrically stimulating the implant by ultrasound-mediated piezoelectric stimulation (USPZ) to promote repair and/or regeneration of tissue malfunction or injury at the implant site.
Nguyen teaches a piezoelectric nanofiber scaffold and further teaches electrically stimulating the implant by ultrasound-mediated piezoelectric stimulation (USPZ) to promote repair and/or regeneration of tissue malfunction or injury at the implant site (paragraph 36). The periods of ultrasound application were selected based on previous research of using ultrasound for bone regeneration.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the stimulation from Kim in view of Ryan in view of Mao with the ultrasound application from Nguyen for the benefit of providing tissue and bone regeneration at a quicker pace.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to THIEN J TRAN whose telephone number is (571)272-0486. The examiner can normally be reached M-F. 8:30 am - 5:30 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Benjamin Klein can be reached at 571-270-5213. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/T.J.T./Examiner, Art Unit 3792
/Benjamin J Klein/Supervisory Patent Examiner, Art Unit 3792
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