DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/07/2025 has been entered.
Applicant’s amendments to the claims and arguments filed on August 7, 2025 have been received and entered. Claim 1 has been amended, while claims 2-8, 10, 16 and 18 have been canceled. The Han’s declaration under 37 CFR 1.132 filed on August 7, 2025 is insufficient to overcome the rejection of claims 1-5, 7-9, 10-11, 12-13 and 14, based upon Sfeir/ Kim, Lih, Lih (2), Gandolfi and Omaghi, applied under 35 U.S.C. 103. The declaration will be discussed in detail below as it applies to the rejection. Claims 1, 9, 11-15 and 17 are pending in the instant application.
Election/Restrictions
Applicant's election with traverse of claims 1-5, 7-14 (group I) in the reply filed on December 23, 2204 was acknowledged. The requirement was deemed proper as discussed in previous office action dated 01/30/2025 and is therefore made FINAL.
Claims 15 and 17 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on December 23, 2024.
Priority
This application is a 371 of PCT/KR2022/003267 filed on 03/08/2022, which claims priority from a foreign application KR10-2021-0030041 filed on 03/08/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Applicant's submission of a certified English translation of KR10- 2021-0030041 priority application to perfect priority filed on April 24, 2025 is acknowledged.
Claims 1, 9, 11-13 and 14 are under consideration.
Withdrawn-Claim Rejections - 35 USC § 103
Claims 1-4, 8-14 were rejected under 35 U.S.C. 103 as being unpatentable over Sfeir (US 20170014548, 1/19/2017)/ Kim et al (US20210052770, dated 02/23/2021, EFD, 1/28/2019), Lih (1, ACS Cent. Sci. 2019, 5, 458−467), Lih (2, ACS Nano, 2018, 12(7). 6917-6925) and Gandolfi et al (Nanomaterials 2020,10, 1-20). Applicant’s amendments to the claim incorporating the limitation of claim 7 obviates the basis of the rejection. Therefore, previous rejection of claims are hereby withdrawn. Applicants’ arguments with respect to the withdrawn rejections are thereby rendered moot.
Maintained- 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, 9, 11-13 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Sfeir (US 20170014548, 1/19/2017)/ Kim et al (US20210052770, dated 02/23/2021, EFD, 1/28/2019), Lih (1, ACS Cent. Sci. 2019, 5, 458−467), Lih (2, ACS Nano, 2018, 12(7). 6917-6925) and Gandolfi et al (Nanomaterials 2020,10, 1-20) and further in view of Omaghi (EP2745849, dated 12/16/2013).
With respect to claims 1, 12-14, Sfeir teaches a composite scaffold comprising magnesium-polymer composite for tissue healing and regeneration, comprising: magnesium particles; and polymer matrix, wherein the magnesium particles are embedded in the polymer matrix selected from group consisting of poly (glycolic acid), poly (L-lactic acid), poly (lactic-co-glycolic acid) or a mixture thereof (see claims 1-3 of ‘548). Sfeir teaches bioactive agents including nucleic acid (DNA) could be incorporated in the composite (see para. 39). Regarding claims 12-14, Sfeir teaches a medical implant comprising said composite discussed above, wherein the implant is selected from the group consisting of plates, meshes, staples, screws, pins, tacks, rods, suture anchors (see claim 12-13). Likewise, Kim teaches composition, comprising: a) a nucleic acid; b) a bone graft; and c) a cationic polymer, wherein a) the nucleic acid and c) the cationic polymer forms a bond which holds b) the bone graft to form an aggregate (claim 1 of ‘770) and wherein nucleic acid could be mixed at varying weight ratio of the polymer (see para. 14, 36) and wherein the nucleic acid is deoxyribonucleic acid (DNA), a ribonucleic acid (RNA), or a mixture thereof (see claim 1), and wherein the polymer is polyethylene amine, poly-L-lysine, and polyallylamine (see para. 19). It is further disclosed that the composition may be implanted to a lesion (see para. 56). Kim provides evidence of optimizing the nucleic acid amount by weight based on 100-part weight of polymer support by disclosing that the nucleic acid and the polymer could be used at a content of 0.001-2% by weight and at a content of 0.001-2% by weight respectively (see para. 45). Sfeir/Kim differs from claimed invention by not disclosing polymer scaffold comprising (i) a magnesium hydroxide that is modified with L-Lactide (limitation of claim 1) (ii) bioactive material that includes a extracellular vesicles and nucleic acid is PDRN(claim 1).
Before the effective filing date of instant application, Lih cure the deficiency by providing motivation to include complex extracellular matrix in the scaffold. Lih teaches ECM has components that are appropriate for the growth and function of the kidney cells, acellular renal ECM has been utilized as a supporting material to biologically functionalize PLGA
scaffolds. The proteins and growth factors remaining in acellular renal ECM could encourage the reconstruction of glomerulus. It is further disclosed that the scaffold with the addition of
Mg (OH)2 and acellular ECM to PLGA scaffolds for effective renal regeneration (Figure 1b). Mg (OH)2 could neutralize the acidic microenvironment induced by the acidic decomposed
products of PLGA, thereby suppressing undesirable inflammatory reactions. The acellular ECM could promote the normal biological function of kidney cells. Thus, this approach may be used to design advanced functional scaffolds to overcome the disadvantages of conventional PLGA scaffolds and effectively induce regeneration of renal tissue with complex biological functions (see page 459, col. 2, para. 2 and 3, fig. 1). Lih (2) teaches aggregated Mg (OH)2 particles in PLGA matrix do not sufficiently neutralize the acidic degradation products. The aggregated Mg (OH) 2 accelerate degradation reaction of PLGA by attacking the backbone of contacting polymer rather than dispersedly and uniformly dissociating into Mg 2+ and OH−ions and neutralizing the acidic byproducts. Lih teaches using oligolactide-grafted Mg (OH) that is modified with L-Lactide leading to prevention of aggregation of Mg (OH) 2 nanoparticles (Figure 1). Lih provide evidence that Mg (OH)2 nanoparticle inherently has a size of 209 ± 101 nm when not modified (page 6918, col. 2, last para. Fig. S1 and S2) (limitation of claim 11).
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The combination of reference differs from claimed invention by not disclosing polymer scaffold comprising bioactive material that includes a mixture of extracellular vesicles (claim 1).
Before the effective filing date of instant application, Gandolfi teaches scaffolds composed of a polymer (PLA) and incorporating different percentages of bioactive materials that were enriched with exosomes secreted from human adipose (fat) derived -mesenchymal stem cells (hAD-MSCs) (limitation of claim 9). The collected exosomes resulted a homogeneous population of cup- or round-shaped vesicles having 110-180 nm diameter and expressing the typical exosome surface markers, such as CD9, CD63, and CD81 [#"]. The results shows that exosomes interacted with hAD-MSCs through membrane-to-membrane fusion, delivering their content into the targeted cells and triggering their biological effect (see page 14, para. 2-3), The combination of references differs from claimed invention by not disclosing DNA fragment is polydeoxyribonucleotide (PDRN).
Omaghi reported use of PDRNs and nucleic acid tissue regeneration because of their ability to stimulate fibroblast metabolism and the production of dermal matrix components (see para. 4-5). Omaghi teaches a composition comprising incorporating PDRN in chitosan and its effect of stimulating cell proliferation necessary for regenerative medicine (abstract, para. 12). Omaghi further teaches preparing the solution containing 15 to 50% mg/ml of PDRN (see claim 8 of ‘849) and mixing in second solution of polymer in varying amount of 1 to 10% W/V.
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to modify the polymer scaffold of Sfeir/Kim by incorporating ECM and Ad-MSC derived exosome as disclosed in Lih (1) and Gandolfi, to produce biodegradable implant, as instantly claimed, with a reasonable expectation of success, before the effective filing date of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. It would have been further prima facie obvious for a person of ordinary skill in the art to modify the polymer scaffold of by modifying the surface of Mg (OH)2 with D-Lactide as disclosed in Lih (2), to overcome the problem associated with acid-induced inflammatory responses associated with biodegradable polymers such as poly(lactide-co-glycolide), by using oligo(lactide)-grafted magnesium hydroxide (Mg(OH)2) nanoparticles (see above or Lih 2 abstract). It would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to modify the polymer scaffold of combination of prior art by substituting DNA in the composition disclosed by Sfeir/Kim with PDRN as disclosed in Omaghi to produce biodegradable implant, as instantly claimed, with a reasonable expectation of success. One of ordinary skill in the art would be motivated to do so because (i) prior art of Gandolfi explicitly reported exosomes are natural mediators in cell–cell communication involved in several physiological processes including neo-angiogenesis, regulation of immune response and extracellular matrix remodeling, affecting cell phenotype, recruitment, proliferation and differentiation (see page 2, para. 3) and (ii) PDRNs are also known to promote angiogenesis in the treatment of wounds and burns, to accelerate the healing of skin micro-lesions and the production of cytokines and growth factors (see para. 6-8). Absent evidence of any unexpected superior results, the limitation of DNA fragment mixture is about 15-part weight to about 20 parts weights based on 100 parts by weight of polymer would be obvious optimization of amount of DNA mixture in the polymer depending on type of polymer support selected for the composition as evident form the teaching of Kim. MPEP2144.05 states “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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 experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). One of skill in the art would have been expected to have a reasonable expectation of success in modifying the scaffold of Sfeir/Kim by incorporating exosome and ECM because prior art successfully reported incorporating exosome scaffold (see Gandolfi) and ECM (Lih(1)) in the nucleic acid/PDRN polymer scaffold. It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith, --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR, 82 USPQ2d at 1396) (available at http: www. uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Response to arguments
Applicant disagree with the rejection arguing claim 1 has been amended to specifically limit the basic nano-ceramic particles to magnesium hydroxide or magnesium oxide and further specify that these particles are surface-modified with L-lactide oligomers. Applicant assert that Applicant also conducted additional experiments submitted herein in a Declaration and also shown below, demonstrating unexpected superior effects of the claimed invention, as compared to the ricinoleic acid (RA) surface treatment disclosed in the reference Lih 2. Applicant argues that while Lih 2 discloses RA surface treatment to overcome aggregation issues of Mg(OH), the claimed invention uses oligo(D,L-lactide) (ODLLA) surface modification, which provides fundamentally different and superior properties. Applicant show that BP/MH-ODLLA composite achieves a remarkable Young's modulus of 4.25 GPa, representing a 38.5% improvement over the unmodified system and a substantial 26.1% improvement over the RA- modified system (see fig. 1 and table 1, pages 2-3 of the declaration and applicant’s argument). Applicant argues that the 26.1% improvement in Young's modulus over RA-modified systems could not have been predicted by a person of ordinary skill in the art, and the synergistic interaction between ODLLA and the biodegradable polymer matrix represents a novel approach that transcends mere aggregation prevention. The structural similarity between ODLLA and the biodegradable polymer matrix creates synergistic effects that are not foreseeable based on the disclosures of the cited references, particularly given that Lih merely describes surface treatment for aggregation prevention, without any suggestion of the enhanced compatibility and mechanical reinforcement achieved through structural similarity to the polymer matrix. Applicant further argues that there is no motivation to select specific multiple elements from multiple unrelated reference with a reasonable expectation of success. Applicants’ arguments have been fully considered, but are not found persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e. uses oligo(D,L-lactide) (ODLLA) surface modification, which provides fundamentally different and superior properties or BP/MH-ODLLA composite achieves a remarkable Young's modulus of 4.25 GPa or mechanical reinforcement achieved through structural similarity to the polymer matrix) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). It should be noted that none of the claim require oligo(D,L-lactide) (ODLLA) surface modification or interaction between ODLLA and the biodegradable polymer matrix as argued by the applicant.
Further, unexpected results have to be commensurate with the scope of the invention. "Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)." In the instant case, specification and examples teaches mixing magnesium hydroxide with L-Lactide in toluene together with stannous octoate (see page 11, last and page 12, para. 1) similar to one disclosed in art of record summarized by the reference of Lih.(2) (see page 6922, col. 2, para. 4). It is emphasized that ODLLA (oligo-D,L-lactic acid) is an oligomer derived from a racemic mixture, which is different from L-lactide, enantiopure monomer as exemplified in the instant application. There is no evidence on record that the unexpected superior resulting from the usage of oligo(D,L-lactide) (ODLLA) surface modification that provides fundamentally different and superior properties could be extended to surface modification of magnesium hydroxide nanoparticle with L-lactide. It is relevant to note that post filing publication of Baek ( Materials 2021, 14, 5869, 1-13, cited as evidence without relying on the rejection) teaches mixing D, L-Lactide, 1-octanol and stannous octoate in toluene to synthesize ODLLA oligomer (see page 3, section 2.2). The instant specification fails to teach mixing D, L-Lactide, 1-octanol and stannous octoate in toluene to synthesize ODLLA oligomer as exemplified in the Han’s declaration. Therefore, applicant’s arguments are commensurate with the scope of the claimed invention. In the instant came none of the claims require use of oligo(D,L-lactide) (ODLLA) surface modification.
In response to applicant's argument that Lih (2) merely describes surface treatment for aggregation prevention, without any suggestion of the enhanced compatibility and mechanical reinforcement achieved through structural similarity to the polymer matrix, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). In the instant case, Lih (2) explicitly teaches modified nanoparticles comprising the Mg(OH)2 surface functionalized with oligomers of lactide significantly reduced the in vivo inflammatory response without altering the degradability rates but improving the mechanical properties of PLGA (see page 6922, col. 1, para. 3). To the extent, Lih(2) teaches mixing magnesium hydroxide nanoparticles and L-LA in toluene together with stannous octoate as a catalyst and reacted in a nitrogen atmosphere (see page 6922, col. 2, para. 4), it is applicable to rejection. A person of skill in the art would be motivated to modify the polymer scaffold composite of Sfeir/Kim as disclosed in Lih (1) and Gandolfi by modifying the surface of Mg (OH)2 with L-lactide as disclosed in Lih (2), to overcome the problem associated with use of Mg (OH) 2 by modifying the surface Mg (OH)2 (i) prevention of aggregation of Mg (OH) 2 nanoparticles and (ii) reduced in vivo inflammatory response without altering the degradability rates (see above), with a reasonable expectation of success.
Therefore, in view of the fact patterns of the instant case, and the ground of rejection outlined by the examiner, applicants’ arguments are not compelling and do not overcome the rejection of record.
Examiner’s note: Applicant’s representative was contacted on November 19, 2025 to inform that declaration filed on 8/7/2025 is not commensurate with the claimed invention. It was indicated that claim recites surface modification with L-Lactide that is different from use of D, L-Lactide oligomer to modify the surface of magnesium hydroxide nanoparticle as exemplified in the declaration. There is no evidence on record that surface modification that provides superior properties with ODLLA could be extended to surface modification with L-lactide. Applicant’s representative will confirm the data and/or make necessary amendments to expedite the prosecution. No agreement was reached.
Conclusion
No claims allowed.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANOOP K. SINGH whose telephone number is (571)272-3306. The examiner can normally be reached Monday-Friday, 8AM-5PM. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571)272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ANOOP K SINGH/ Primary Examiner, Art Unit 1632