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 . Claims included in the prosecution are claims 1, 2, 4-8, 14 and 47-50.
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 06/23/2026 has been entered.
Applicants' arguments, filed 06/23/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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.
1. Claims 1, 2, 4, 8 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Jeyapalina et al. (WO 2020/146646 A1, Jul. 16, 2020) (hereinafter Jeyapalina) in view of Coleman et al. (US 2015/0037387, Feb. 5, 2015) (hereinafter Coleman) and Chaari et al. (Elaboration and characterization of fluorapatite ceramic with controlled porosity, Jan 2009) (hereinafter Chaari).
Jeyapalina discloses an implantable scaffold including a fluoridated apatite structure sized and shaped for implantation in an animal (¶ [0005]). The scaffold may include pores (¶ [0033]). The fluoridated apatites include one or more of fluorohydroxyapatite or fluorapatite that is sintered at a sintering temperature selected to provide a desired surface morphology for the scaffold. The scaffolds may include dopants composed to initiate and sustain bone growth and integration, such as an implantee’s own stem cells (adipose derived stem cells (ASCs)), bone morphogenetic protein-2 (BMP-2), tissues, combinations thereof, or the like (¶ [0026]). The scaffold may include one or more dopants (¶ [0034]). Doping the fluoridated apatite particles may include adding one or more dopants to the plurality of fluoridated apatite particles prior to forming the coherent body, or coating at least a portion of the coherent body with one or more dopants after forming the coherent body (¶ [0079]). The scaffold may exhibit a porosity of 30% to 70% (¶ [0075]). The pores may be filled with one or more dopants (¶ [0034]).
Jeyapalina differs from the instant claims insofar as not disclosing a stromal vascular fraction adhered to the fluoridated apatite structure.
However, Coleman discloses a cell-seeded tissue graft comprising a reparative cell preparation seeded onto a porous scaffold, wherein the tissue graft is prepared by isolating a fresh stromal vascular fraction (SVF) from an adipose tissue of a patient; applying the fresh SVF cells to the porous scaffold, and rinsing the porous scaffold to eliminate cells that are unbound by the porous scaffold (claim 1). Adipose derived stromal cells seeded onto carrier bioprosthetics facilitated formation of new bone in an animal model (¶ [0008]). The cell seeded tissue grafts may be utilized to treat one or more of: wound healing, burns, bone fractures, cosmetic defects, cartilage damage, tendon damage, ulcers, fistulas, hernias, retinal degeneration, treatment of ischemic disease, nerve injury, aneurysms, bladder wall repair, intestinal injury, and repair and reconstruction of vessels (¶ [0020]).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. Jeyapalina discloses wherein the scaffold comprises one or more dopants composed to initiate and sustain bone growth. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated a stromal vascular fraction from an adipose tissue onto the scaffold of Jeyapalina since it is a known and effective dopant for initiating and sustaining bone growth as taught by Coleman.
The combined teachings of Jeyapalina and Coleman do not teach wherein the fluoridated apatite structure has a pore size ranging from about 100 µm to about 1500 µm.
However, Chaari discloses wherein in recent years, attention was particularly placed on the fabrication of bioceramics with “porous” configuration because the porous network allows tissue to infiltrate, which further enhances the implant-tissue attachment. In a porous form, hydroxyapatite ceramics can be colonized by bone tissue with the same characteristics as peri-implanted tissues. For colonization of the pores to take place, they must be larger than 50-100 µm or even 250-300 µm according to some researchers (page 219, left column, second paragraph). Chaari further discloses production of fluorapatite bioceramics wherein the pore sizes were typically distributed in the range of 50-300 µm (page 226, conclusion).
Accordingly, since the pores of the fluoridated apatite structure include dopants composed to initiate and sustain bone growth and integration, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the fluoridated apatite structure to have a pore size ranging from 50-300 µm motivated by the desire to allow colonization of the pores to take place as taught by Chaari. One of ordinary skill in the art would have had a reasonable expectation of success since this pore size is suitable for fluoridated apatite structures as taught by Chaari.
2. Claims 5 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Jeyapalina et al. (WO 2020/146646 A1, Jul. 16, 2020) (hereinafter Jeyapalina) in view of Coleman et al. (US 2015/0037387, Feb. 5, 2015) (hereinafter Coleman), Chaari et al. (Elaboration and characterization of fluorapatite ceramic with controlled porosity, Jan. 2009) (hereinafter Chaari), and further in view of Si et al. (Adipose-derived stem cells: Sources, potency, and implications for regenerative therapies, Mar. 25, 2019) (hereinafter Si).
The teachings of Jeyapalina, Coleman, and Chaari are discussed above. Jeyapalina, Colemen, and Chaari do not teach wherein the stromal vascular fraction includes perivascular cells, leukocytes, endothelial cells, fibroblasts, and progenitor stem cells.
However, Si discloses wherein a stromal vascular fraction (SVF) containing adipose-derived stem cells (ASCs), pre-adipocytes, endothelial cells, fibroblasts, endothelial progenitor cells, resident monocytes/macrophages, pericytes (i.e., perivascular cells), endothelial progenitor cells (i.e., progenitor stem cells), vascular smooth muscle cells, leukocytes, lymphocytes, and erythrocytes (page 2, left column section 1.1).
As discussed above, it would have been obvious to one of ordinary skill in the art to have incorporated a stromal vascular fraction from an adipose tissue onto the scaffold of Jeyapalina. Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have incorporated the stromal vascular fraction of Si onto the scaffold of Jeyapalina since it is a known and effective stromal vascular fraction as taught by Si.
3. Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Jeyapalina et al. (WO 2020/146646 A1, Jul. 16, 2020) (hereinafter Jeyapalina) in view of Coleman et al. (US 2015/0037387, Feb. 5, 2015) (hereinafter Coleman) and Chaari et al. (Elaboration and characterization of fluorapatite ceramic with controlled porosity, Jan. 2009) (hereinafter Chaari), and further in view of Yayon (US 2006/0147547, Jul. 6, 2006).
The teachings of Jeyapalina, Coleman, and Chaari are discussed above. Jeyapalina, Coleman, and Chaari do not teach at least one metal substitute substituted into the fluoridated apatite structure.
However, Yayon discloses a bone-enhancing composite material that may be used as an implant (abstract). The composite comprises synthetic apatite (¶ [0032]). The synthetic apatite may contain cation or anion substitutions. Zinc may be added to partly replace the calcium ions (¶ [0037]). The incorporation of additional or different divalent ions imparts on the composition certain properties that may be advantageous to bone repair and growth (¶ [0114]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have substituted zinc into the fluoridated apatite structure motivated by the desire to impart to the structure properties that may be advantageous to bone repair and growth as taught by Yayon.
4. Claims 47-50 are rejected under 35 U.S.C. 103 as being unpatentable over Jeyapalina et al. (WO 2020/146646 A1, Jul. 16, 2020) (hereinafter Jeyapalina) in view of Yayon (US 2006/0147547, Jul. 6, 2006).
Jeyapalina discloses an implantable scaffold including a fluoridated apatite structure sized and shaped for implantation in an animal (¶ [0005]). The scaffold may include pores (¶ [0033]). The fluoridated apatites include one or more of fluorohydroxyapatite or fluorapatite that is sintered at a sintering temperature selected to provide a desired surface morphology for the scaffold. The scaffolds may include dopants composed to initiate and sustain bone growth and integration, such as an implantee’s own stem cells (adipose derived stem cells (ASCs)), bone morphogenetic protein-2 (BMP-2), tissues, combinations thereof, or the like (¶ [0026]). The scaffold may include one or more dopants (¶ [0034]). Doping the fluoridated apatite particles may include adding one or more dopants to the plurality of fluoridated apatite particles prior to forming the coherent body, or coating at least a portion of the coherent body with one or more dopants after forming the coherent body (¶ [0079]). The scaffold may exhibit a porosity of 30% to 70% (¶ [0075]). The pores may be filled with one or more dopants (¶ [0034]).
Jeyapalina differs from the instant claims insofar as not disclosing at least one metal substitute substituted into the fluoridated apatite structure.
However, Yayon discloses a bone-enhancing composite material that may be used as an implant (abstract). The composite comprises synthetic apatite (¶ [0032]). The synthetic apatite may contain cation or anion substitutions. Zinc may be added to partly replace the calcium ions (¶ [0037]). The incorporation of additional or different divalent ions imparts on the composition certain properties that may be advantageous to bone repair and growth (¶ [0114]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have substituted zinc into the fluoridated apatite structure motivated by the desire to impart to the structure properties that may be advantageous to bone repair and growth as taught by Yayon.
In regards to instant claim 47 reciting wherein about 0.5 molar % to about 5 molar % of calcium in the fluoridated apatite structure is replaced with zinc, since the incorporation zinc ions by replacing calcium ions imparts on the composition certain properties that may be advantageous to bone repair and growth, it would have taken no more than the relative skills of one of ordinary skill in the art through routine experimentation to have arrived at the claimed amount calcium ion replacement depending on the bone repair and growth effect desired. 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 experimentation. See MPEP 2144.05(II)(A).
Response to Arguments
Applicant argues that fluoridated apatite structures with a porosity of 45% to 60% and a pore size ranging from about 100 µm to about 1500 µm are believed to promote the bone ingrowth and the differentiation of SVF cells as demonstrated in the experiments (Paragraph [00103]).
The Examiner does not find Applicant’s argument to be persuasive. Applicant has not shown with objective evidence wherein a porosity of 45% to 60% and a pore size ranging from about 100 µm to about 1500 µm promote the bone ingrowth and the differentiation of SVF cells. There are no showings comparing various porosities and pore sizes. Mere conclusory statements in the specification, unsupported by objective evidence, are entitled to little weight when the PTO questions the efficacy of those statements. In re Greenfield, 571 F.2d 1185, 197 U.S.P.Q. 227, 229 (C.C.P.A. 1978). Therefore, Applicant’s argument is merely speculative and not persuasive. Furthermore, as discussed in the rejection, Jeyapalina teaches a porosity of 30% to 70%. Applicant has not shown wherein the claimed porosity of 45% to 60% is advantageous over the porosity of Jeyapalina. Additionally, as discussed in the rejection, Chaari teaches wherein pore size affects colonization taking place in pores and wherein pores must be larger than 50-100 µm for colonization. Therefore, one of ordinary skill in the art would expect pore size to affect promotion of bone ingrowth and the differentiation of SVF cells in pores. Applicant has not shown wherein the specific pore size claimed is unexpected. As such, Applicant’s argument is unpersuasive.
Applicant argues that the experimental examples of the present Application demonstrated that a 2 molar % substitution (i.e., 2% of the calcium ions are replaced by zinc ions) provided effective antimicrobial effects, but also taught that the amount should be less than 5 molar % to prevent unwanted secondary phase formations in the apatite structure.
The Examiner does not find Applicant’s argument to be persuasive. Applicant’s examples do not compare various amounts of zinc substitution. The examples all use 2%. Thus, Applicant has not provided objective evidence showing wherein the claimed range is critical and unexpected. Mere conclusory statements in the specification, unsupported by objective evidence, are entitled to little weight when the PTO questions the efficacy of those statements. In re Greenfield, 571 F.2d 1185, 197 U.S.P.Q. 227, 229 (C.C.P.A. 1978). As such, Applicant’s argument is unpersuasive.
Applicant argues that the Examiner is suggesting that the skilled person would start from a ceiling of 100 molar % substitution (i.e., every calcium ion is replaced by a zinc ion). This would not meaningfully guide the skilled person to the ceiling amount recited in claim 47.
The Examiner does not find Applicant’s argument to be persuasive. As discussed above, Applicant has not shown wherein less than 5% substitution is critical. Also, the Examiner is not suggesting starting from a ceiling of 100 molar % substitution. The Examiner had stated that by knowing the amount of calcium ions originally there, one of ordinary skill in the art would have known an upper amount of zinc from which to optimize from. Thus, one of ordinary skill in the art may start at any amount less than 100% molar substitution and continue to add zinc until a desired amount that imparts advantageous bone repair and growth is reached. As such, Applicant’s argument is unpersuasive.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 11, 2, 4-8, 14 and 47-50 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 47, 48, 51 and 52, of copending Application No. 17/420,589 in view of Yayon (US 2006/0147547, Jul. 6, 2006), Coleman et al. (US 2015/0037387, Feb. 5, 2015) (hereinafter Coleman), Chaari et al. (Elaboration and characterization of fluorapatite ceramic with controlled porosity, Jan. 2009) (hereinafter Chaari), and Jeyapalina et al. (WO 2020/146646 A1, Jul. 16, 2020) (hereinafter Jeyapalina).
The pending claims differ from the copending claims insofar as reciting at least one metal substitute substituted into the fluoridated apatite structure, a stromal vascular fraction, a porosity of 45% to 60%, and a pore size of from about 100 µm to about 1500.
However, Yayon discloses a bone-enhancing composite material that may be used as an implant (abstract). The composite comprises synthetic apatite (¶ [0032]). The synthetic apatite may contain cation or anion substitutions. Zinc may be added to partly replace the calcium ions (¶ [0037]). The incorporation of additional or different divalent ions imparts on the composition certain properties that may be advantageous to bone repair and growth (¶ [0114]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have substituted zinc into the fluoridated apatite structure motivated by the desire to impart to the structure properties that may be advantageous to bone repair and growth as taught by Yayon.
However, Coleman discloses a cell-seeded tissue graft comprising a reparative cell preparation seeded onto a porous scaffold, wherein the tissue graft is prepared by isolating a fresh stromal vascular fraction (SVF) from an adipose tissue of a patient; applying the fresh SVF cells to the porous scaffold, and rinsing the porous scaffold to eliminate cells that are unbound by the porous scaffold (claim 1). Adipose derived stromal cells seeded onto carrier bioprosthetics facilitated formation of new bone in an animal model (¶ [0008]). The cell seeded tissue grafts may be utilized to treat one or more of: wound healing, burns, bone fractures, cosmetic defects, cartilage damage, tendon damage, ulcers, fistulas, hernias, retinal degeneration, treatment of ischemic disease, nerve injury, aneurysms, bladder wall repair, intestinal injury, and repair and reconstruction of vessels (¶ [0020]).
The copending claims recites wherein the scaffold comprises one or more bone growth dopants. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated a stromal vascular fraction from an adipose tissue since it is a known and effective dopant for initiating and sustaining bone growth as taught by Coleman.
However, Chaari discloses wherein in recent years, attention was particularly placed on the fabrication of bioceramics with “porous” configuration because the porous network allows tissue to infiltrate, which further enhances the implant-tissue attachment. In a porous form, hydroxyapatite ceramics can be colonized by bone tissue with the same characteristics as peri-implanted tissues. For colonization of the pores to take place, they must be larger than 50-100 µm or even 250-300 µm according to some researchers (page 219, left column, second paragraph). Chaari further discloses production of fluorapatite bioceramics wherein the pore sizes were typically distributed in the range of 50-300 µm (page 226, conclusion).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the fluoridated apatite structure to have a pore size ranging from 50-300 µm motivated by the desire to allow colonization of the pores to take place as taught by Chaari.
Jeyapalina discloses an implantable scaffold including a fluoridated apatite structure sized and shaped for implantation in an animal (¶ [0005]). The scaffold may include pores (¶ [0033]). The scaffold may exhibit a porosity of 30% to 70% (¶ [0075]). The pores may be filled with one or more dopants (¶ [0034]).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art to have formulated the fluoridated apatite structure to have a porosity of 30% to 70% since this is a known and effective porosity for a fluoridated apatite structure sized and shaped for implantation in an animal as taught by Jeyapalina.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicant’s arguments have been considered but are moot because a new rejection necessitated by Applicant’s amendment has been made.
Conclusion
Claims 1, 2, 4-8, 14 and 47-50 are rejected.
Claims 15, 22 and 29 have been withdrawn.
No claims are allowed.
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/TRACY LIU/Primary Examiner, Art Unit 1614
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