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 .
Detailed Action
Restriction/Election
Applicant’s election without traverse of group I, claims 1-12 in the reply filed on 04/17/26 is acknowledged. Applicant’s election of Species 1: TLS for the lignin derivative, Species 2: CaO₂ for the inorganic peroxide, Species 3: gelMA for the carrier is also acknowledged.
Claims 13-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/17/26.
Claim Rejections - 35 USC § 112, indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
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.
Claim 12 is 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 pre-AIA the applicant regards as the invention.
Claim 12 recites the term “substantially” which is a relative term which renders the claim indefinite. The term “substantially” 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 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 1-6 and 11-12 are rejected under 35 U.S.C. 103 as being unpatentable over Nelson et al. (US PG Pub. 2021/0069378A1).
Nelson et al. nano-cellulose containing bioinks, see title. The reference teaches methacrylated gelatin, methacrylated gellan gum, see [0162]. Lignin derivatives such as sulfonated lignin is taught, see [0308]. Use of calcium peroxide is taught, see [0299].
Thus, the reference teaches lignin derivative as sulfonated lignin, calcium per oxide and a carrier. This combination is not in a single embodiment. However, all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results of having a composition comprising one or more lignin derivatives, at least one inorganic peroxide and a carrier, see MPEP 2143 part (I)(A).
Claims 1-3 and 6-12 are rejected under 35 U.S.C. 103 as being unpatentable over Wang, (“Hyaluronic acid-coated PEI-PLGA nanoparticles mediated co-delivery of doxorubicin and miR-542-3p for triple negative breast cancer therapy” (hereinafter referenced as Wang et al.) in view of Liu et al., (“Development of Novel Lignin-Based Targeted Polymeric Nanoparticle Platform for Efficient Delivery of Anticancer Drugs” (hereinafter referenced as Liu), in view of Olsson et al. (US 2014/0080992 A1) and further in view of Makadia et al. (Poly Lactic-co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier (hereinafter referenced as Makadia)), Niu et al. (US PG Pub. 2023/0302191A1) and Atala et al. (AU2013203151B2).
Wang teaches a hyaluronic acid (HA)-decorated polyethyleneimine-poly)D,L-lactide-co-glycolide) (PEI-PLGA) nanoparticle system for targeted co-delivery of doxorubicin (DOX) and miR-54-3p for triple negative breast cancer (TNBC) therapy (abstract). Furthermore, Wang teaches ester bonds, (page 413, left col., last para.), hydrophobic Dox (page 418, left col., 1st para.), and hyaluronic acid (HA)-decorated polyethyleneimine-poly)D,L-lactide-co-glycolide) (PEI-PLGA) nanoparticles dispersed as monodispersed particles with a well-defined spherical core-shell structure (page 414, right col., last para.).
Wang does not teach lignin in core-shell nanoparticles.
Liu teaches lignin-based targeted nanoparticles (NPs) platform, folic acid-polyethylene glycol-alkaline lignin conjugates (FA-PEG-AL), via self-assembly for delivery of anti-cancer drug (hydroxyl camptothecin, HCPT). Notably, Liu teaches that these lignin-based nanoparticles had particles size (~150 nm) and exhibited excellent biocompatibility, high drug loading efficiency, and prolonged blood circulation time (~7-fold of free HCPT, and enhanced cellular uptake (~5-fold of free HCPT) (Abstract). Liu teaches lignin-based nanoparticles (abstract) component of the instant composition.
Liu teaches alkaline lignin (page 1731, paragraph 2.1). As noted in specification, paragraph (0022), lignin can be obtained commercially as alkaline lignin or as sodium lignosulfonate (both of which are more hydrophilic than native lignin), and either form may be used in practicing this instant invention. Liu teaches lignin-based nanoparticles had moderate particle size (~150 nm) (abstract).
Olsson et al. teach graft co-polymers of lignin and poly(lactic acid) (lignin-g-PLA copolymer), methods of preparing these polymers (abstract). Olsson et al. teach Lignin-g-PLA copolymers have controllable PLA chain lengths and, in some embodiments, the PLA-chain length is controlled by varying one or more of lignin/lactide ratio and pre-acylation such as pre-acetylation of the lignin (paragraph 0007) and the ability to control the grafted PLA chain lengths and the degree of chain extension/cross-linking offers access to a broad spectrum of materials ranging from thermoplastics to thermosets (paragraph 0009). Furthermore, Olsson et al. disclose the structure and properties of the lignin-g-PLA can be tuned by changing the Stereoforms (L, D, or DL) of lactides and by utilizing different lignin sources (paragraph 0017) and in various embodiments, the use of co-monomers other than a lactide is without limitation (paragraph 0019). However, Olsson et al. do not disclose Lignin with PLGA. An article of interest by Makadia discloses polyester PLGA is a copolymer of poly lactic acid (PLA) and poly glycolic acid (PGA). It is the best defined biomaterial available for drug delivery with respect to design and performance. Poly lactic acid contains an asymmetric α-carbon which is typically described as the D or L form in classical stereochemical terms and sometimes as R and S form, respectively. The enantiomeric forms of the polymer PLA are poly D-lactic acid (PDLA) and poly L-lactic acid (PLLA). PLGA is generally an acronym for poly D,L-lactic-co-glycolic acid where D- and L- lactic acid forms are in equal ratio. In order to design a better controlled drug delivery device or system, it is essential to understand the physical, chemical and biological properties of PLGA. The physicochemical properties of optically active PDLA and PLLA are nearly the same. In general, the polymer PLA can be made in highly crystalline form (PLLA) or completely amorphous (PDLA) due to disordered polymer chains. PGA is void of any methyl side groups and shows highly crystalline structure in contrast to PLA. PLGA can be processed into almost any shape and size, and can encapsulate molecules of virtually any size. It is soluble in wide range of common solvents including chlorinated solvents, tetrahydofuran, acetone or ethyl acetate (pages 2-3, paragraphs 2.1-2.2). Thus, one of ordinary skill in the art would have reasonable expectation of a better drug delivery system when substituting PLA with PLGA due to the above described properties. Through routine experimentation, one would be able to envisage to replace PLA with PLGA with the desired lignin to PLGA ratio of instant invention.
It would have been obvious to one of ordinary skill in the art before the effective filing date of he claimed invention to use the drug delivery system of PLGA core-shell nanoparticles with hydrophobic drug molecule as taught by Wang and incorporate lignin-based targeted polymeric nanoparticle platform of Liu to improve biocompatibility, high drug loading efficiency and prolonged blood circulation and enhanced cellular uptake. One would have been motivated to do so because improving a drug delivery system to achieve the desired therapeutic effects, better targeting site of action with enhanced tissue permeability and prolonged drug distribution in blood stream and biocompatibility translate to improved clinical outcomes and better tolerability of cancer drugs, for example. The combine teachings of Olsson and Makadia renders the possibility of graft co-polymers of lignin and poly(lactic acid) (lignin-g-PLA copolymer), and substituting PLGA for PLA and tune to the desired ratios. One of skill in the art would be able to optimize the ratio of lignin to PLGA to have the co-polymers perform in the desired dispersion, interaction and polymerization in the composition.
One of ordinary skill in the art would have been motivated to do this because all references are drawn to core-shell nanoparticles compositions comprising graft polymer lignin and PLGA with a hydrophobic molecule, and it is obvious to combine prior art elements according to known methods to yield predictable results. Please see MPEP 2141. One of ordinary skill in the art would have had a reasonable expectation of success to include the components in their corresponding weight ratio and nanoparticle diameter ranges as taught by each of the references and produce a functional core-shell nanoparticle comprising lignin-PLGA drug delivery composition.
The references discussed above do not teach use of inorganic peroxide.
Niu et al. teaches use of calcium peroxide as oxygen-generating system, wherein the localized oxygenation can avoid systemic hyperoxia while accelerating chronic wound healing, see [0151].
Atala et al. teaches use of various active ingredients including oxygen generating calcium peroxide and doxorubicin, see description. The reference teaches a method of treating hypoxic tissue in need thereof, comprising contacting a composition to the hypoxic tissue in a hypoxia-treatment effective amount, the composition comprising a biodegradable polymer and an inorganic peroxide incorporated into the polymer, preferably in solid form (and optionally a radical trap or decomposing catalyst incorporated into and/or onto the polymer in solid form). In some embodiments the hypoxic tissue is in vivo in a subject in need of the treatment. In some embodiments, the tissue is wound tissue and the composition is administered in an amount effective to facilitate the healing of the wound tissue. In some embodiments, the method further comprises the step of concurrently treating the wound tissue with negative pressure wound therapy. In some embodiments, the tissue is afflicted with an anaerobic infection and the composition is administered in an amount effective to treat the infection. In some embodiments, the tissue is cancer tissue and the composition is administered in an amount effective to treat the cancer (alone, or in combination with one or more additional therapeutic agents). In some embodiments, the composition is in the form of a sheet material, and the contacting step is carried out by contacting the sheet material to the tissue. In some embodiments, the composition is in the form of injectable microparticles, and the contacting step is carried out by injecting the microparticles into the tissue. In some embodiments, the composition is in the form of a spray, and the contacting step is carried out by spraying the composition onto the tissue. In some embodiments, the composition is in the form of a surgical or paramedical aid, and the contacting step is carried out by contacting the aid to the tissue. A second aspect of the invention is a composition comprising, consisting of, or consisting essentially of; (a) from 50 or 70 to 99 percent by weight of a biodegradable polymer; and (b) from 0.1 to 30 percent by weight of inorganic peroxide incorporated into the polymer in solid form; and (c)optionally from 0.1 to 30 percent by weight of a radical trap or peroxide decomposition catalyst incorporated into the polymer in solid form; and WO 2008/124126 PCT/US2008/004502 -3 (d) optionally from 0.001 to 5 percent by weight of at least one additional active agent (e.g., antibiotics, growth factors, steroids, antineoplastic agents, etc.). The composition may be in the form of sheet material, injectable microparticles, other shaped articles or scaffolds, etc. A still further aspect of the invention is, in a method of culturing mammalian tissue in vitro on a solid support or scaffold, the improvement comprising utilizing as the scaffold a composition comprising a biodegradable polymer and an inorganic peroxide incorporated into the polymer in solid form so that oxygenation of the tissue is thereby enhanced. Brief Description of the Drawings Figure 1. Oxygen release from POG film, in vitro. In the formulation used the release of oxygen follows a sigmoidal curve with a high rate of oxygen release during the first 24 hours. The control material, PLGA, did not show any oxygen release. Figure 2: Flap Necrosis. Graph expressing the necrosis in percent of total flap size. At early time points, 2 and 3 days, the SPO group showed a significant better flap survival with less necrosis, when compared to the control group, see description.
Thus, it would have been obvious to one of ordinary skill to have utilized the inorganic peroxide for oxygenation purposes motivated by the teachings of Niu et al. during wound healing into the core of nanoparticle of Wang et al. and replace or add with doxorubicin for added benefit of providing oxygen during the therapy motivated by the teachings of Atala et al.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SNIGDHA MAEWALL whose telephone number is (571)272-6197. The examiner can normally be reached Monday thru Friday; 8:30 AM to 5PM.
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/SNIGDHA MAEWALL/Primary Examiner, Art Unit 1612
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