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 .
Election/Restrictions
Applicant’s election of group I and the species of bone morphogeneticprotein 2 as the therapeutic agent in the reply filed on 04/30/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 15-16 and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 04/30/2025.
Claims 1-14 and 29-31 are being examined on the merits.
Claim Objections
Claim 9 is objected to because of the following informalities: The claim recites the term “corilagen” and it appears that the proper spelling for the term is “corilagin”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 11 and 29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Alexndru Bri et. al. (from IDS, US20100255447A1).
Regarding claims 1-3, Bri discloses a coating comprising micro and/or nano materials deposited on a surface of a medical implantable device which can be delivered into a human/animal host organism (see claims 1-5) and wherein the coating comprises a natural or synthetic polymer (see claim 8). Bri discloses wherein the coating micro or nanoparticles comprises of bone morphogeneticprotein (see claims 16 and 29). Bri also discloses the use of electrospray to deposit the material (see 0007).
Regarding claim 11, Bri discloses wherein the coating is about 0.5 nm which is within the range disclosed (see claim 9).
Regarding claim 29, Bri discloses wherein the therapeutic agent is bone morphogeneticprotein (see claim 29 and 0011).
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-3, 10-11, 14 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Alexndru Bri et. al. (from IDS, US20100255447A1).
Regarding claims 1-3, Bri discloses a coating comprising micro and/or nano materials deposited on a surface of a medical implantable device which can be delivered into a human/animal host organism (see claims 1-5) and wherein the coating comprises a natural or synthetic polymer (see claim 8). Bri discloses wherein the coating micro or nanoparticles comprises of bone morphogeneticprotein (see claims 16 and 29). Bri also discloses the use of electrospray to deposit the material (see 0007).
Regarding claim 10, Bris discloses a coating comprising micro and/or nano materials deposited on a surface of a medical implantable device which can be delivered into a human/animal host organism (see claims 1-5) and wherein the coating comprises a natural or synthetic polymer (see claim 8). Bri discloses wherein the coating micro or nanoparticles comprises of bone morphogeneticprotein (see claims 16 and 29). Bri also discloses the use of electrospray to deposit the material (see 0007). Bris also discloses that the coating comprises of one or more layers or nanoparticles and/or microparticles wherein a core made of one nanoparticle material; and at least one layer surrounding said core, wherein said layer comprises… any combination of natural or synthetic polymer (see 0020).
Regarding claim 11, Bri discloses wherein the coating is about 0.5 nm which is with the range disclosed (see claim 9).
Regarding claim 14, Bri discloses wherein the coating is an allograft (see claim 8).
Regarding claim 29, Bri discloses wherein the therapeutic agent is bone morphogeneticprotein (see claim 29 and 0011).
Bri does not specifically teach that the coating is for bone allograft however Bri teaches wherein the coating is for allograft hard tissue (see claim 8) and wherein the coating is to be used for bone (see 0003, claim 23, 29-30, 36 etc.).
Therefore it would have been obvious given the prior art and before the effective filling date to use Bri’s invention for a bone allograft as this is what Bri teaches. In another embodiment, said layers comprise hydroxyapatite, wherein said layers degrade over time and release nanoparticles and/or microparticles of hydroxyapatite for stimulating bone formation adjacent to a surface of said device (see 0015) and teaches “In a further embodiment, the growth factor is a bone morphogeneticprotein capable of promoting bone formation adjacent to or on the surface of a device” (see 0011). Thus, it can be understood that the invention is intended to be used for such purposes as coating bone grafts.
Claims 4-6 and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Alexndru Bri et. al. (from IDS, US20100255447A1) as applied to claims 1-3, 10-11 and 14 above, and further in view of Nishimura wt. al. (from IDS, US20030082784A1).
Bri teaches methods of preparing a coated bone graft, however is silent on the bone stimulating agent being BMP-2 or fragment thereof.
Nishimura’s general disclosure is to a novel peptide having osteogenic activity (see abstract).
Regarding claim 4 and 30, Nishimura teaches a bone stimulating agent being BMP-2 (see 0048 and 0051) and teaches using the same peptide fragment as instantly claimed (see below).
Regarding claim 5 and 31, Nishimura teaches a peptide having an amino acid sequence represented by SEQ ID NO:1 of the instant application (see Test example, 0063, (Lys Ile Pro Lys Ala Ser Ser Val Pro Thr Glu Leu Ser Ala Ile Ser Thr Leu Tyr Leu)) and having osteogenic activity (see claim 1).
Regarding claim 6, Nishimura teaches a styrene-divinyl benzene polymer in use with preparing the bone graft peptide formulations (see 0021) and this would be a hydrophobic polymer.
Therefore it would have been obvious given the prior art and before the effective filling date to use BMP-2 or a fragment thereof with SEQ ID NO:1 of the instant invention because Nishimura teaches that this fragment has osteogenic activity and using this for material as a bone stimulating agent for coating of a bone graft would have been prima facie obvious.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Alexndru Bri et. al. (from IDS, US20100255447A1) and Nishimura wt. al. (from IDS, US20030082784A1) as applied to claims 1-6, 10-11, 14 and 30-31 above, and further in view of Archana Swami et. al. (US20150125391A1).
Bri and Nishimura teach the methods of preparing a coated bone graft with the use of hydrophobic polymers, however are silent on the polymer being that of poly(lactide-co-glycolide).
Swami’s general disclosure is to bone and metal targeted polymeric nanoparticles (see abstract).
Swami teaches “Bone and metal-targeted polymeric nanoparticles have three main components: 1) a targeting element that selectively binds to bone, minerals, and/or metal ions; 2) a “stealth layer” to allow the nanoparticles to evade cell mediated immune response, including uptake by the reticuloendothelial system (the “RES”); and 3) a biodegradable polymeric material forming an inner core, which can carry therapeutic, prophylactic, or diagnostic agents. Preferred nanoparticles contain a blend of targeting element-amphiphilic polymer conjugate and amphiphilic polymer that optimizes the ligand density on the surface of the nanoparticle to provide improved targeting of the nanoparticle. The ratio of targeting element-polymer conjugate to polymer can also be optimized to improve the half-life of the nanoparticles in the blood of the subject. The nanoparticles exhibit prolonged, sustained release of therapeutic agents loaded into the particles” (see 0011-0012).
Swami teaches “The nanoparticles can contain one more of the following polyesters: homopolymers including glycolic acid units, referred to herein as “PGA”, and lactic acid units, such as poly-L-lactic acid, poly-D-lactic acid, poly-D,L-lactic acid, poly-L-lactide, poly-D-lactide, and poly-D,L-lactide, collectively referred to herein as “PLA”, and caprolactone units, such as poly(ε-caprolactone), collectively referred to herein as “PCL”; and copolymers including lactic acid and glycolic acid units, such as various forms of poly(lactic acid-co-glycolic acid) and poly(lactide-co-glycolide) characterized by the ratio of lactic acid:glycolic acid, collectively referred to herein as “PLGA”; and polyacrylates, and derivatives thereof” (see 0063).
Therefore it would have been obvious given the prior art and before the effective filling date to use poly(lactide-co-glycolide) as a polymer in the invention taught by Bri because as Swami teaches, poly(lactide-co-glycolide) is a suitable polymer which can be used to bind to bone.
Claims 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Alexndru Bri et. al. (from IDS, US20100255447A1) as applied to claims 1-3, 10-11 and 14 above, and further in view of Fan Yang et. al. (Anti-Schistosomiasis Liver Fibrosis Effect of Corilagin Through Interacting the IL-13/miR-21/smads Signaling Pathway in Vitro and in Vivo, The Lancet, Sept 17, 2018) and Ying Huang et. al. (MicroRNA-21: A Central Regualtor of Fibrotic Diseases Via Various Targets, Current Pharmaceutical Design, 2015, 21, 2236-2242).
Bri teaches methods of preparing a coated bone graft, however is silent on the therapeutic agent consists of an anti-fibrotic agent being that of corilagin.
Yang teaches “no matter in normal, miR-21 up- or down-regulated LX2 cells, corilagin could inhibit the mRNA level of miR-21 and CTGF and promote smad7 mRNA level (P < 0.01 or 0.05). Meanwhile, corilagin could significantly reduce the protein level of CTGF, p-smad1, p-smad2, psmad2/3, smad4, TβR Ⅰ and α-SMA，and promote smad7 protein level (P <0.05 or 0.01). Corilagin could decrease serum IL-13 and SCAg level (P < 0.01 or 0.05), and also reduce the degree of liver fibrosis in pathological manifestations. Interpretation: Corilagin could inhibit schistosomiasis-induced hepatic fibrosis through the potential drug intervention targets in IL13/miR21/smads pathway, which might serve as an anti-fibrosis agent…” (see abstract).
Although Yang teaches that corilagin can inhibit fibrosis in hepatic cell lines, Huang’s disclosure is relied upon to show how the same mir-21/smad pathways discussed by Yang are beneficial for control over fibrosis.
Huang’s article discusses miR-21 as a regulator of fibrotic disease (see abstract).
Huang teaches that “MicroRNAs (miRNAs) are small non-coding RNA molecules that diversely regulate physiological and pathophysiological processes by specifically binding to different regions of targeting messenger RNAs (mRNAs). Fibrosis is characterized by the abnormal proliferation of fibroblasts and the deposition of the extracellular matrix (ECM). Both clinical and experimental animal studies have revealed that aberrant expression of miRNAs is closely associated with the development of fibrotic diseases. microRNA-21 (miR-21) is a ubiquitously expressed miRNA that is traditionally considered to be an oncogenic miRNA (oncomiR). Recent studies have demonstrated that elevated expression of miR-21 may play a vital role in the development of fibrosis by promoting the proliferation of interstitial fibroblasts and increasing the abnormal deposition of the ECM. In this review, we comprehensively summarize the role of miR-21 in tissue fibrosis. Furthermore, we highlight miR-21 as a potential diagnostic and prognostic marker and therapeutic target for fibrosis diseases” (see abstract).
Additionally, “miR-21 is a ubiquitously expressed miRNA in human tissues. The important role of miR-21 in the pathogenesis of fibrotic diseases has been generally demonstrated by both clinical and basic evidences. The accumulated data suggest a promising idea that sequence-specific inhibition of miR-21 may provide a novel therapeutic implication in fibrotic disease” (see conclusion and perspectives, page 2240).
Therefore it would have been obvious given the prior art and before the effective filling date to use anti-fibrotic agent such as corilagin in the invention taught by Bri because corilagin is known as an anti-fibrotic agent which can inhibit miR-21 levels thus helping to reduce fibrosis of interstitial tissues and decreasing abnormal deposition of the ECM as discussed by Huang and Yang.
There would have been a reasonable expectation of success in using corilagin as an anti-fibrotic agent for the invention taught by Huang because both Yang and Huang teach how it can inhibit miR-21 which in turn would decrease fibrosis.
Claims 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Alexndru Bri et. al. (from IDS, US20100255447A1) as applied to claims 1-3, 10-11, 14 and 29 above, and further in view of Jingwei Xieand Sunil Kumar Boda (from IDS, WO2019209762A1), hereinafter Xie.
Bri teaches methods of preparing a coated bone graft, however is silent on the freeze drying, lyophilized or mineralized of the synthesized coated bone graft.
Xie’s general disclosure is to the use of Nanofiber segments and nanofiber microspheres as injectable scaffolds for biomedical engineering (see background of the invention).
Xie teaches of electrospray(ed) nanofibers (see claims 1-2), wherein the nanofibers (coating) are mineralized, comprise of bone morphogenetic protein (see claim 25), freeze-dried and/or lyophilized (see claim 28), and for the purpose of periodontal bone loss (see claims 34 and 37).
Xie teaches “The nanofiber segments and nanofiber microspheres of the instant invention may comprise a material that enhances water absorption; may be crosslinked and/or thermally treated; may be mineralized; may comprise one or more agents or compounds such as therapeutic agents; and/or may comprise cells and/or tissue, or any combination of any one, two, three, four, or five of these features”
“For example, the nanofiber structures may be used to enhance wound healing, build tissue constructs, promote tissue regeneration (e.g., bone regeneration)..” (see summary of the invention, first and second para.).
Xie teaches that “mineralization, for example, with hydroxyapatite, can enhance the adhesion of osteogenic precursor cells in vitro and in vivo”
Therefore it would have been obvious given the prior art and before the effective filling date to mineralize lyophilize and/or freeze-dry the coating in the invention taught by Bri, because these components are taught in the art. It would have been obvious to freeze-dry/lyophilize the coating because this would help preserve the coating components and it would have been useful to mineralize the coating especially given that it is for the purpose for a bone graft as mineralization is needed for bone deposition.
Conclusion
Currently no claims are allowed.
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JACOB A BOECKELMANExaminer, Art Unit 1655
/TERRY A MCKELVEY/Supervisory Patent Examiner, Art Unit 1655