DETAILED ACTION
Claims 1, 5-7, 12-14, 16-17, 19, 21-22, 26-30, 34-36 are currently pending and under examination.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of mixture of pure alginate and zwitterionically-modified alginate, cells producing insulin and nanofiber wall in the reply filed on 09/26/2025 is acknowledged.
No claims are withdrawn as a result of the species election.
Priority
The instant application is a national stage entry of PCT/US2021/025492, filed 04/02/2021, which claims priority to provisional application 63/004,331, filed 04/02/2020.
Information Disclosure Statement
Applicant’s Informational Disclosure Statement, filed on 09/30/2022, 11/16/2022, 05/22/2024 and 08/30/2024 has been considered. Please refer to Applicant's copy of the 1449 submitted herein.
Claim Rejections - 35 USC § 112 (b)
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, 5-7, 26-30 and 34-36 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 contains the limitation of 1:1000 to 1000:1 (v/v) in instant claim 1. The parenthesis regarding the ratio makes it unclear if the v/v is required or is optional. Thus, instant claim 1 has unclear meats and bounds as it is unclear if the ratio is required to be v/v or if the v/v is optional.
Claim 6 contains the limitation “the interior wall”, which does not have antecedent basis. Instant claim 1 contains the limitation an interior nanofiber wall. The limitation of “the interior wall” does not properly refer back to the interior nanofiber wall in instant claim 1.
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.
Claim(s) 1, 5-7, 26-30 and 34-36 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2017/0258852 in view of US 2016/0324793.
Regarding claim 1, the limitation of an implantable therapeutic delivery system comprising: a nanofiber core substrate having proximal and distal ends, said nanofiber core substrate having an interior nanofiber wall defining an internal space extending longitudinally along the core substrate with one or more therapeutic agents positions within the internal space and a hydrogel surrounding said nanofiber core substrate, wherein said hydrogel comprises 0.1 to 20% of an alginate mixture, said alginate mixture comprising zwitterionically modified alginate and pure alginate in a ratio of 1:1,000 to 1000:1 (v/v) is met by the ‘852 publication teaching implantable therapeutic delivery system. The therapeutic delivery system comprises a substrate, an inner polymeric coating that surrounds the substrate and an outer hydrogel coating that surround said inner polymeric coating. One or more therapeutic agents are positions in the outer hydrogel coating (abstract). Nylon nanofibers and alginate hydrogel is taught ([0036]-[0037], [0054]) wherein chemically modified alginate is taught including zwitterionic polymer [0076].. A nanofibrous core substrate having one or more internal spaces suitable for compartmental encapsulation of one or more types of cells. An outer biocompatible polymeric coating surrounds the nanofibrous substrate system [0072]. Nanofibrous microtubes are taught with alginate forming a thin layer surrounding the microtube ([0145]-[0146]).
Regarding claims 5 and 7, the limitation of wherein the interior nanofiber wall of the nanofiber core substrate forms a tube having a diameter of 0.1mm to 30 cm is met by the ‘852 publication teaching the inner tube diameter of the nanofiber tube being 300 um to 3mm [0146].
Regarding claim 6, the limitation of wherein the interior wall has a thickness of 1um to 5mm is met by the ‘852 publication teaching the microtubes have an inner diameter of 300 um to 3mm and the nanofiber size is between 10 nm and 10 um for the electrospun nanofiber membrane. The properties are taught to be tunable ([0142], [0146]). As MPEP 2144.05 recites “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 optimization”.
Regarding claim 26, the limitation of wherein an elongated polymeric scaffold is positioned within internal space of the nanofiber core substrate is met by the ‘852 publication teaches extracellular matrix proteins and cells being dispersed in multiple compartments of the nanofibrous microtubes ([0143], [0145]-[0146]).
Regarding claims 27-29, the limitation of wherein said internal space of the nanofiber core substrate is compartmentalized into two or more sub-internal spaces by one or more internal nanofiber walls is met by multiple compartments can be engineered into a single NHM, which can be used for complex cell encapsulation ([0037], [0143], Figures 2A-2B). Insulin is taught to be used in the implantable system ([0058], [0060]).
Regarding claim 30, the limitation of wherein said proximal and distal ends of the nanofiber core substrate are sealed is met by the ‘852 publication teaching a closed core device (Figure 1b).
Regarding claim 34, the limitation of an implantable therapeutic delivery system wherein the hydrogel surrounding the nanofiber core substrate is crosslinked and interlocked to the nanofiber core substrate is met by the ‘852 publication teaching crosslinking of the alginate by the nanofibers ([0036], [0054]).
Regarding claim 35, the limitation of wherein the hydrogel surrounding the nanofiber core substrate has a thickness of 1 nm to 5nm wherein the standard deviation in thickness of the hydrogel or biocompatible polymer coating around the entirely of the nanofibers core substrate is less 100% is met by the ‘852 publication teaching the process of coating the substrate is by dip coating or immersing the substrate into the polymeric solution and can be repeated one or more times to increase the thickness of the polymeric coating, which in turn will enhance mechanical strength and size of the system [0090] wherein the alginate hydrogel is 70 um diameter [0111], thus teaching the coating thickness is an optimizable parameter. The coating is taught to be relatively uniform [01112], thus teaching a not totally uniform coating meeting the limitation of less than 100% standard deviation.
Regarding claim 36, the limitation of the hydrogel surrounding the nanofiber core substrate comprises one or more biologically active agents selected form a group which includes protein, peptide, small molecule, combinations thereof is met by the ‘852 publication teaching the hydrogel comprising one or more therapeutic agents [087], wherein the therapeutic agent may be proteins, peptides, antibodies, etc. [0056].
The ‘852 does not specifically teach the ratio of 1:1000 to 1000:1 (claim 1).
The ‘793 publication teaches covalently modified alginate polymers, possessing enhanced biocompatible and tailed physiologic chemical properties. Covalently modified alginates are useful as matrix for the encapsulation and transplantation of cells (abstract) including implantation of said cells [0003]. Chemically modified ionically croslinkable alginates with improved biocompatible and tailored physiochemical properties, including gel stability, pore size and hydrophobicity/hydrophilicity is taught [0011]. Modified alginate capsules revealed that modified alginates may result in abnormally shaped capsules wen crosslinking using conditions defined for unmodified. Effort to improve the capsule morphology formation methods or use with modified alginate microparticle were devices wherein modified alginates and alginate were blended to yield improved morphology and ability ([0100]-[0101]). The modified alginate are taught to lower foreign body response than unmodified alginate [0028].
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use a combination of pure alginate and zwitterionically modified alginate in the implantable devices taught by the ‘852 publication because the ‘793 publication teaches that it is known to use a blend of modified and unmodified alginate in implantable compositions. One of ordinary skill in the art before the filing date of the claimed invention would be motivated to use a combination of modified and unmodified alginate as the ‘793 publication teaches a blend of modified and unmodified alginate may yield improved morphology and ability. One of ordinary skill in the art would be motivated to optimize the ratio of pure and zwitterionically modified alginate in order to obtain the desired properties such as improved morphology and shaping. One ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as the ‘852 publication teaches combination of hydrogel polymers and teaches alginate and zwitterionic alginates.
Claim(s) 12-14, 16-17, 19, 21-22 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2017/0258852 in view of US 2006/0094320 and WO 2014/152906.
Regarding claim 12, the limitation of an implantable therapeutic delivery system comprising a nanofiber core substrate having proximal and distal ends, said nanofiber core substrate defined by an inner nanofiber layer and an outer nanofiber layer surrounding the inner nanofiber layer, wherein the inner nanofiber layer has a nanofiber structure that differs from the nanofiber structure of the outer layer, said nanofiber core substrate further comprising an internal space surrounded by the inner nanofiber layer of the substrate, with one or more therapeutic agents portioned within internal space, and biocompatible polymer counting surrounding said nanofiber core substrate is met by the ‘852 publication teaching implantable therapeutic delivery system. The therapeutic delivery system comprises a substrate, an inner polymeric coating that surrounds the substrate and an outer hydrogel coating that surround said inner polymeric coating. One or more therapeutic agents are positions in the outer hydrogel coating (abstract). Nylon nanofibers and alginate hydrogel is taught ([0036]-[0037], [0054]) wherein chemically modified alginate is taught including zwitterionic polymer [0076].. A nanofibrous core substrate having one or more internal spaces suitable for compartmental encapsulation of one or more types of cells. An outer biocompatible polymeric coating surrounds the nanofibrous substrate system [0072]. Nanofibrous microtubes are taught with alginate forming a thin layer surrounding the microtube ([0145]-[0146]).
Regarding claim 14, the limitation of wherein the nanofiber substrate is a cylindrical tube or conical tube is met by the ‘852 publication demonstrates a cylinder (Figures 1).
Regarding claim 16, the limitation of wherein the inner nanofiber layer and outer nanofiber layer independently have a diameter of 1 nm to 50 um is met by the ‘852 publication teaching the electrospun nanofibers have a fiber size of 10 nm to 10 um [0142].
Regarding claim 17, the limitation of wherein the inner nanofiber layer and the outer nanofiber layer independently have one or both of the following including a nanofiber density of 0.01 g/cm3 to 1.5 g/cm3 and/or an average thickness of 1um to 5mm is met by the ‘852 publication teaching the microtubes have an inner diameter of 300 um to 3mm and the nanofiber size is between 10 nm and 10 um for the electrospun nanofiber membrane. The properties are taught to be tunable ([0142], [0146]). As MPEP 2144.05 recites “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 optimization”.
Regarding claim 19, the limitation of wherein one or both of the inner nanofibers layer and/or the outer nanofiber layer comprise pores, said pores having a diameter of 1 nm to 50 um is met by the ‘852 publication teaching an interconnected pore structure of about 1um and tunable properties [0142].
Regarding claim 21, the limitation wherein the inner and outer nanofiber layers of the core substrate have a combined thickness of 1um to 5mm is met by the ‘852 publication teaching the microtubes have an inner diameter of 300 um to 3mm and the nanofiber size is between 10 nm and 10 um for the electrospun nanofiber membrane. The properties are taught to be tunable ([0142], [0146]). As MPEP 2144.05 recites “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 optimization”.
Regarding claim 22, the limitation of wherein the nanofiber core substrate is characterized by one or more of the following having a length of 0.5 cm to 1000m, comprising one or more biologically active agents including protein, peptide, small molecule is met by the ‘852 publication teaching two or more sub-internal spaces by one or more internal nanofiber walls is met by multiple compartments can be engineered into a single NHM, which can be used for complex cell encapsulation ([0037], [0143], Figures 2A-2B). Insulin is taught to be used in the implantable system ([0058], [0060]).
The ‘852 publication does not specifically an inner nanofiber layer and outer nanofiber layer that differs (claim 12) wherein the nanofiber core substrate comprises one or more middle nanofiber layers positioned between the inner and outer nanofiber layers of the substrate and differs from the inner and outer nanofiber layers (claim 13).
The ‘320 publication teaches a gradient material comprising at least two types of nanofibers disturbed non-uniformly through the material to form one or more gradients. The at least two types of nanofibers combine to form a plurality of layers. The nanofibers can be electrospun fibers and have a gradient in the planar and/or thickness directions (abstract). The at least two types of fibers may be deposited substantially simultaneous in an overlapping regions or may combined to form a plurality of layers and may be of any type [0006]. Nylon is taught as an electrospun fiber type [0008]. The different types of fibers can be produced by varying methods to alter specific measurable properties to create different types of fibers. Gradient materials were taught by varying the electrospinning conditions such as speed being varied during the operation, allowing for varying amounts of fibers to be deposited [0065]. Multiple gradient nanofiber material can be laminated to another layer known to provide strength [0085]. Medical implants are taught [0046].
The ‘906 publication teaches multiple layers of nanofiber scaffolds allow the use of polymers with varying pore size and strength through a single scaffold. The presence of layer of different scaffold materials allow for the multiple layers with a pore size gradient applied through the sidewall starting from the innermost layer to the biggest pores in the outermost layers. This allows for the delivery of cells of different sizes to the scaffolds. The multilayered scaffold comprise at least three layers or more including and outer, at least one middle and an inner layer [0013]. The layer may comprise the same or different biodegradable polymers [0015]. Use in implants is taught [0028]. Adjustment of electrospinning allows for adjustment in fiber diameter and alignment for cell infiltration. Pore sizes can also be adjusted. Multiple different polymers and blends may be used to create the ideal mechanical and degradative features for tissue engineering. These alterations in scaffold structure allow for improved cell-scaffold interactions [0042].
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to use a multilayered gradient nanofiber structure to form in the nanofiber membranes of the ‘852 publication because the ‘852 publication teaches the nanofiber structure to be formed by electrospinning, have an interconnected porous structure and tunable material properties such as biodegradability, strength and wettability and the ‘320 publication and the ‘906 publication both teach layered gradient a nanofiber structures formed by electrospinning, wherein the use of the gradient layered structure may be used to optimize the properties such as pore sizes, mechanical and degradable features and cell-scaffold interactions. It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to create a layered nanofiber structure formed by electrospinning to obtain the desired properties of the nanofiber membrane based on the teachings of the ‘852 publication, the ‘320 publication and the ‘906 publication. One of ordinary skill in the art before the filing date of the claimed invention would have a reasonable expectation of success as the ‘852 publication, the ‘320 publication and the ‘906 publication are all directed to nanofiber structures formed by electrospinning which may be used in implants.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNDSEY MARIE BECKHARDT whose telephone number is (571)270-7676. The examiner can normally be reached Monday-Thursday 9am to 4pm and Friday 9am to 2pm.
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/LYNDSEY M BECKHARDT/Examiner, Art Unit 1613