DETAILED ACTION
Receipt is acknowledged of applicant’s Amendment/Remarks filed 8/4/2026.
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 .
Status of the Claims
Claims 1, 3-8, 11 and 12 have been amended. Claim 1 is cancelled. No claims are newly added. Accordingly, claims 1-9, 11 and 12 remain pending in the application and are currently under examination.
Withdrawn Rejections
Applicant’s amendment renders the rejection of claims 1-5 and 12 under 35 USC 103 over Lerouge, Amodei, Lin, Ritman, Narayanan, Guo and Runge moot. Specifically, the references are silent to the newly added limitations, “20 to 50 % by weight polycaprolactone fumarate combined with 50 to 80 % by weight poly (glycolic acid) or poly lactic-co-glycolic acid” and “from 0.2 to 1.5% w/v hyaluronic acid (HA)”. Thus, said rejection has been withdrawn. However, after further consideration a new grounds of rejection is made under 35 USC 103 over Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge and Li with additional evidentiary references.
Applicant’s amendment renders the rejection of claims 6, 7 and 10 under 35 USC 103 over Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge and Das moot. Specifically, the references are silent to the newly added limitations, “20 to 50 % by weight polycaprolactone fumarate combined with 50 to 80 % by weight poly (glycolic acid) or poly lactic-co-glycolic acid” and “from 0.2 to 1.5% w/v hyaluronic acid (HA)”. Thus, said rejection has been withdrawn. However, after further consideration a new grounds of rejection is made under 35 USC 103 over Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Li and Das with additional evidentiary references.
Applicant’s amendment renders the rejection of claim 8 under 35 USC 103 over Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Das, Massaro and Li moot. Specifically, the references are silent to the newly limitations, “20 to 50 % by weight polycaprolactone fumarate combined with 50 to 80 % by weight poly (glycolic acid) or poly lactic-co-glycolic acid” and “from 0.2 to 1.5% w/v hyaluronic acid (HA)”. Thus, said rejection has been withdrawn. However, after further consideration a new grounds of rejection is made under 35 USC 103 over Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Li, Das and Massaro with additional evidentiary references.
Applicant’s amendment renders the rejection of claim 9 under 35 USC 103 over Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge and CN ‘447 moot. Specifically, the references are silent to the newly added limitations, “20 to 50 % by weight polycaprolactone fumarate combined with 50 to 80 % by weight poly (glycolic acid) or poly lactic-co-glycolic acid” and “from 0.2 to 1.5% w/v hyaluronic acid (HA)”. Thus, said rejection has been withdrawn. However, after further consideration a new grounds of rejection is made under 35 USC 103 over Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Li and CN ‘447 with additional evidentiary references.
Applicant’s amendment renders the rejection of claim 11 under 35 USC 103 over Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Das, Massaro, Li and Jayasuriya moot. Specifically, the references are silent to the newly added limitations, “20 to 50 % by weight polycaprolactone fumarate combined with 50 to 80 % by weight poly (glycolic acid) or poly lactic-co-glycolic acid” and “from 0.2 to 1.5% w/v hyaluronic acid (HA)”. Thus, said rejection has been withdrawn. However, after further consideration a new grounds of rejection is made under 35 USC 103 over Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Li, Das and Jayasuriya with additional evidentiary references.
Maintained Objections/Rejections
Duplicate Claims
Applicant is advised that should claim 3 be found allowable, claim 4 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Response to Arguments
Applicant's arguments, filed 8/4/2026, do not present any arguments regarding the duplicate claim warning.
The duplicate claim warning is still applicable and, thus, maintained.
New Objections/Rejections
In light of Applicant’s amendments, the following rejections have been newly added:
Specification
The disclosure is objected to because of the following informalities: Paragraph [0072] of the instant specification recites, “PLGS” which appears to be a typographical error of “PLGA”.
Appropriate correction is required.
Claim Objections
Claim 6 is objected to because of the following informalities: said claim recites, “wherein the carrier solution comprises one or more of chondroitin sulfate (CS) or methyl cellulose (MC)”. To improve clarity, it is suggested that “further” is inserted prior to “comprises”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 5 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 5 recites, “wherein the bone graft containment device comprises at least one of the poly-l-lactic acid (PLLA)…”. Claim 5 depends from claim 1. Claim 1 sets out that the containment device comprises a resin comprising from 20 to 50% by weight polycaprolactone fumarate combined with 50 to 80% by weight poly (glycolic acid) or poly lactic-co-glycolic acid. The claim is indefinite because it is unclear if the PLLA is further limiting the poly lactic of the poly lactic-co-glycolic acid or if the PLLA is an additional ingredient.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3-5 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 3 and 4 both recite that the bone graft containment device comprises PCLF; however, PCLF is a required component recited in parent claim 1. Accordingly, claims 3 and 4 do not properly further limit the subject matter of claim 1.
Claims 5 recites, “wherein the bone graft containment device comprises at least one of the poly-l-lactic acid (PLLA) or poly lactic-co-glycolic acid; however, poly lactic-co-glycolic acid is a required component recited in parent claim 1. Accordingly, claim 5 does not properly further limit the subject matter of claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 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.
Claims 1-6 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Lerouge et al. (US 2017/0360912 A1, Dec. 21, 2017, hereafter as “Lerouge”) in view of Amodei (US 2011/0172826 A1, Jul. 14, 2011, hereafter as “Amodei”), Lin et al. (WO 2012/118846 A1, Sep. 7, 2012, hereafter as “Lin”), Ritman et al. (US 2010/0221347 A1, Sep. 2, 2010, hereafter as “Ritman”), Narayanan et al. (“Poly (Lactic Acid)-Based Biomaterials for Orthopaedic Regenerative Engineering”, Adv Drug Deliv Rev. 2016 December 15; Volume 107, pp. 1–76; hereafter as “Narayanan”), Gou et al. (CN 113941029 A, Jan. 18, 2022, machine translation, hereafter as “Gou”), Runge et al. (US 2013/0331869 A1, Dec. 12, 2013, hereafter as “Runge”) and Li et al. (“Arthroscopic debridement of the osteoarthritic knee combined with hyaluronic acid (Orthovisc®) treatment: A case series and review of the literature”, J Orthop Surg Res., 2008 Sep 17, 3:43; hereafter as “Li”) as evidenced by Sigma Aldrich - PCLF (see PTO-892), Yaszemski et al. (“Reformulating polycaprolactone fumarate to eliminate toxic diethylene glycol: Effects of polymeric branching and autoclave sterilization on material properties”, Acta Biomaterialia, 8 (2012) 133-143; hereafter as “Yaszemski”) and Sigma Aldrich - PLGA (see PTO-892).
The instant invention is drawn to a system for delivering a bone graft composition comprising: a bone graft composition comprising: a recombinant factor comprising one or more interleukin-1 receptor antagonist protein (IRAP) or platelet derived growth factor (PDGF); and a carrier solution comprising a solvent, from 0.2 to 1.5% w/v hyaluronic acid (HA) or two-dimensional silicate nanomaterial, and a cross-linked 3D printed bone graft containment device for delivering the bone graft composition, wherein the 3D printed bone graft containment deice is solvent-etched such that the 3D printed bone graft containment device is free of un-crosslinked polymer and comprises a resin comprising from 20 to 50 % by weight polycaprolactone fumarate combined with 50 to 80 % by weight poly (glycolic acid) or poly lactic-co-glycolic acid, wherein the composition is a thermoresponsive gel or shear-thinning gel.
Regarding instant claim 1, Lerouge teaches a hydrogel comprising chitosan and two weak bases having different pKb values (abstract). Lerouge taches that immediately after preparation, the chitosan-based gel solution is flowable and becomes a gel after a gelation time, the gelation time being temperature dependent ([0006]. Said gel can further comprise a therapeutic agent such as interleukin-1 receptor antagonists (IRAP) and platelet-derived growth factor (PDGF) ([0027] and [0029]). Lerouge teaches that the gel may further comprise a biopolymer excipient such as chondroitin sulfate, hyaluronic acid, as well as combinations thereof ([0035]-[0036]). Lerouge also teaches that the chitosan based gel can include mineral particles such as silicates for the purpose of promoting bone regeneration ([0080]-[0081] and [0373]). Lerouge teaches that the invention can treat bone or cartilage defect by injecting the chitosan based gel into said defect ([0123], [0208]-[0209]) and [0373]. Lerouge specifically teaches that the gel is a thermoresponsive gel ([0263]).
Lerouge is silent to an embodiment combining each of claimed elements, however it would have been prima facie obvious to combine said elements with a reasonable expectation of success because Lerouge teaches that each are combinable and suitable for inclusion in the chitosan-based gel composition.
Lerouge is also silent to a bone graft containment device.
Amodei teaches stimuli-responsive gels including hyaluronic acid, chondroitin sulphate, thermoresponsive gels, etc. can be incorporated into a bone cage (i.e., containment device) ([0378]). Amodei teaches that the bone cage can be used in repairing bone ([0250], [0251] and [0257]).
Lerouge and Amodei are both drawn to gel compositions that can be used for the purpose of repairing bone, thus, it would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to include the gel of Lerouge in a bone graft containment device such as a bone cage as suggested by Amodei with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Amodei teaches that loading a bone cage with a bone repair gel is suitable for treating a bone defect.
Lerouge and Amodei are silent to the bone graft containment device being crosslinked and 3D printed (instant claim 1). Lerouge and Amodei are also silent to 20 to 50% by weight polycaprolactone fumarate combined with 50 to 80 % by weight poly lactic-co-glycolic acid (instant claims 1 and 3-5).
It is noted that the limitation “3D printed” in claim 1 deems said claim and its dependent claims as product-by-process claims and as such, determination of patentability is based on the product itself, not by the method in which it is made. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process (MPEP 2113).
Lin teaches a cage for facilitating fusion of bones, such as vertebrae, or fusion of adjacent bone surfaces, wherein the cage comprises a biodegradable polymeric material, an osteoconductive mineral coating and a bioactive agent (abstract). Lin teaches the particular biodegradable polymers, polycaprolactone, polylactide, polyglycolide, poly(lactide-glycolide), poly(propylene fumarate), poly(caprolactone fumarate), polyethylene glycol, poly(glycolide-co-caprolactone) as well as mixtures and combinations thereof ([0049] and [0067]; claim 17). Lin also teaches that cage fabrication can occur via various methods including Fused Deposition Modeling (FDM) which is a known 3D printing method ([0076]-[0077]). PCLF comprises bio-compatible poly(caprolactone) units which provide flexibility and fumarate repeat units provide cross linking ability without adding any toxic cross-linkers as evidenced by Sigma Aldrich – PCLF. PCLF is also known to be more slowly degradable than over polyesters as evidenced by Yaszemski (page 142; right col., 1st para.). PLGA can be tuned by varying the ratio of lactide to glycolide monomers in order to obtain different degrees of crystallinity, thermal transitions, solubility, and rates of degradation as evidenced by Sigma Aldrich – PCLF.
Ritman teaches materials and methods related to tissue scaffolds for use in replacing or augmenting various tissues in the body, wherein said tissues include bone (abstract; [0065]). In a particular embodiment, Rittman teaches a scaffolding material comprising polypropylene fumarate (PPF) and polycaprolactone fumarate (PCF) that can be crosslinked and its mechanical properties can be efficiently modulated by varying the composition of PPF in PPF/PCLF blends ([0074]-[0077]).
Narayanan teaches methods of fabricating scaffolds for tissue regeneration including polylactic acid (PLA)-based structures by a 3D printing process that exhibited excellent structural integrity with superior thermo-mechanical characteristics which was achieved by cross-linking the extruded PLA structures (paragraph bridging pages 6-7). Narayanan also teaches such structures can be utilized for orthopedic applications including the vertebra (page 3, 3rd paragraph; paragraph bridging pages 6-7). Narayanan also teaches that PLA-based materials include PLLA and PLGA (page 2, last para. – page 3, 2nd para.).
The references are all drawn to compositions and devices for the purpose of repairing bone, thus, it would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to include the particular combination of polymers, poly(caprolactone fumarate) and poly(lactide-glycolide) into the bone cage of Amodei as suggested by Lin with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Lin teaches that said polymers are suitable bone cage materials for treating bone and combining equivalents known for the same purpose is prima facie obvious (MPEP 2144.06). It would have also been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to optimize the concentrations of each polymer and arrive at the claimed amounts by way of routine experimentation with a reasonable expectation of success because Lin teaches a finite number of polymers to include PCLF and PLGA as well as polymer mixtures are suitable and PCLF and PLGA are each known to have particular properties wherein modifying the amounts of PCLF and PLGA will effectively alter the properties of the combination (i.e., crosslinkable, flexibility, degradability, solubility, etc.) and allow for tunability depending on the desired properties of said combination. It is the normal desire of scientists or artisans to improve upon what is already generally known including determining the optimum combination of percentages (MPEP 2144.05). It would have further been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to 3D print and cross-link said polymers as suggested by Lin/Ritman/Narayanan with a reasonable expectation of success. A skilled artisan would have been motivated to do so because the prior art teaches that such processes of crosslinking and 3D printing are suitable for said materials in the fabricating of devices in orthopedic applications and because cross-linking, more specifically, improves the mechanical properties of said polymeric materials.
The references are silent to the limitation, “wherein the 3D printed bone graft containment deice is solvent-etched such that the 3D printed bone graft containment device is free of un-crosslinked polymer”.
Guo teaches a 3D printed cross-linked polymeric nerve conduit that is soaked in a solvent to remove the non-crosslinked polymer following the step of 3D printing the nerve conduit (abstract; page 3, paragraph 7; page 4, paragraph 4).
Runge teaches a conductive polymer composite composed of polycaprolactone fumarate-polypyrrole (PCLF-PPy) for nerve regeneration that is made by a process comprising pouring a PCLF mixture in a mold and cross-linking the PCLF, the resulting PCLF scaffold is removed from the mold and submerged in MeCl2 (a solvent) to remove uncrosslinked materials (abstract; [0045]).
The references are all drawn to compositions and devices for the purpose of repairing or regenerating tissue, thus, it would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to solvent etch the 3D printed bone containment device of Lin/Ritman/Narayanan in order to remove uncrosslinked polymer as suggested by Guo/Runge with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Guo and Runge teach that removing uncrosslinked material from a crosslinked polymeric device using a solvent is routine and conventional in biomedical applications. A skilled artisan would have reasonably expected a 3D printed crosslinked bone containment device free of uncrosslinked polymer.
The references are silent to “0.2% to 1.5% w/v of hyaluronic acid HA”.
Li teaches treating individuals with osteoarthritic knees via injecting hyaluronic acid into their joints, resulting in reduced pain (review). Li teaches injecting a 6 mL solution containing 90 mg (1.5 % w/v) of hyaluronic acid into the joint (page 2, col 2, para 2). In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In the instant case, because Li’s hyaluronic acid dosage concentration of 1.5% w/v overlaps with the instantly claimed hyaluronic acid dosage concentration of 0.2-1.5% w/v, a prima facie case of obviousness exists. See MPEP § 2144.05(I).
The references are all drawn to compositions and devices for the purpose of repairing bone, thus, it would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to include 0.2% to 1.5% w/v of HA into the invention of Lerouge/Amodei/Lin/Ritman/Narayanan/Guo/Runge, as suggested by Li, with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Li teaches therapeutically effective dosages of hyaluronic acid locally delivered into the joints of arthritic patients. A skilled artisan would have reasonably expected that inclusion of the claimed amounts of HA into the invention of Lerouge/Amodei/Lin/Ritman/Narayanan/Guo/Runge would be useful in the treatment of bone disease/disorders.
Regarding instant claim 2, Amodei further teaches that the bone cage can have variable pore sizes which allows for bone restructuring ([0292]).
Regarding instant claim 6, Lerouge, as discussed above, teaches that the gel may further comprise a biopolymer excipient such as chondroitin sulfate, hyaluronic acid, as well as combinations thereof ([0035]-[0036]). While Lerouge does not teach a particular embodiment combining chondroitin sulfate and hyaluronic acid, it would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to combine chondroitin sulfate and hyaluronic acid, as suggested by Lerouge, with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Lerouge teaches that said biopolymer excipients are suitable materials for treating bone defects and combining equivalents known for the same purpose is prima facie obvious (MPEP 2144.06).
Regarding instant claim 12, Lerouge, as discussed above, teaches the inclusion of therapeutic agents such as interleukin-1 receptor antagonists (IRAP) and platelet-derived growth factor (PDGF) ([0027] and [0029]). The instant specification states,
[00065] Both IRAP and PDGF are key components for PRP and BMAC. IRAP provides the anti-inflammatory environment to prevent or reduce HA and extracellular matrix (ECM) degradation. PDGF can promote the chondrocyte growth and proliferation to accelerate new ECM synthesis at the injection site.
Therefore, in light of the specification, the inclusion of IRAP would necessarily reduce HA and ECM degradation and the inclusion of PDGF would necessarily promote chondrocyte growth and proliferation to accelerate new ECM synthesis. Since Lerouge teaches the inclusion of IRAP and PDGF, a skilled artisan would reasonably expect that a composition containing IRAP and/or PDGF would necessarily possess the properties of reducing HA and ECM degradation and/or promote chondrocyte growth and proliferation to accelerate new ECM synthesis. A composition and its properties are inseparable (MPEP 2112.1(II)).
Thus, the combined teachings of Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge and Li render the instant claims prima facie obvious.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Lerouge et al. (US 2017/0360912 A1, Dec. 21, 2017, hereafter as “Lerouge”) in view of Amodei (US 2011/0172826 A1, Jul. 14, 2011, hereafter as “Amodei”), Lin et al. (WO 2012/118846 A1, Sep. 7, 2012, hereafter as “Lin”), Ritman et al. (US 2010/0221347 A1, Sep. 2, 2010, hereafter as “Ritman”) and Narayanan et al. (“Poly (Lactic Acid)-Based Biomaterials for Orthopaedic Regenerative Engineering”, Adv Drug Deliv Rev. 2016 December 15; Volume 107, pp. 1–76; hereafter as “Narayanan”), Gou et al. (CN 113941029 A, Jan. 18, 2022, machine translation, hereafter as “Gou”), Runge et al. (US 2013/0331869 A1, Dec. 12, 2013, hereafter as “Runge”) and Li et al. (“Arthroscopic debridement of the osteoarthritic knee combined with hyaluronic acid (Orthovisc®) treatment: A case series and review of the literature”, J Orthop Surg Res., 2008 Sep 17, 3:43; hereafter as “Li”) as evidenced by Sigma Aldrich - PCLF (see PTO-892), Yaszemski et al. (“Reformulating polycaprolactone fumarate to eliminate toxic diethylene glycol: Effects of polymeric branching and autoclave sterilization on material properties”, Acta Biomaterialia, 8 (2012) 133-143; hereafter as “Yaszemski”) and Sigma Aldrich - PLGA (see PTO-892), as applied to claim 1 above, and further in view of Das et al. (“Laponite-based Nanomaterials for Biomedical Applications: A Review”, Current Pharmaceutical Design, 2019, 25, 424-443; hereafter as “Das”).
The claimed invention is described above.
The references teach the elements discussed above including that the chitosan based gel of Lerouge can include mineral particles such as silicates for the purpose of promoting bone regeneration ([0080]-[0081] and [0373]) as well as a biopolymer excipient such as chondroitin sulfate (CS) or hyaluronic acid (HA) ([0035]-[0036]).
Regarding instant claim 7, the references are silent to the particular silicate, a two-dimensional silicate nanomaterial such as Laponite® (LAP) (i.e., a synthetic smectite clay).
Das teaches the inclusion of LAP in hydrogels enhanced the mechanical properties of the polymer matrix used in tissue engineering applications (page 432). Das also teaches LAP has shown bone healing properties (page 433, left col. 1st full para.). Das further teaches the on of LAP with polysaccharides such as chitosan, alginate and methyl cellulose has improved brittleness of said polysaccharides (page 433, right col., 1st full para.).
The references are all drawn to compositions and devices for the purpose of repairing bone, thus, it would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to include a two-dimensional silicate nanomaterial such as Laponite® into the invention of Lerouge/Amodei/Lin/Ritman/Narayanan/Guo/Runge/Li, as suggested by Das, with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Das teaches that LAP improves the properties of polymers/polysaccharides when combined with said polymers/polysaccharides and because LAP possesses bone healing properties. A skilled artisan would have reasonably expected that the addition of LAP into the invention of Lerouge/Amodei/Lin/Ritman/Narayanan/Guo/Runge/Li would further provide bone healing properties and improve the properties of polymer/polysaccharide carrier.
Thus, the combined teachings of Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Li and Das render the instant claims prima facie obvious.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Lerouge et al. (US 2017/0360912 A1, Dec. 21, 2017, hereafter as “Lerouge”) in view of Amodei (US 2011/0172826 A1, Jul. 14, 2011, hereafter as “Amodei”), Lin et al. (WO 2012/118846 A1, Sep. 7, 2012, hereafter as “Lin”), Ritman et al. (US 2010/0221347 A1, Sep. 2, 2010, hereafter as “Ritman”), Narayanan et al. (“Poly (Lactic Acid)-Based Biomaterials for Orthopaedic Regenerative Engineering”, Adv Drug Deliv Rev. 2016 December 15; Volume 107, pp. 1–76; hereafter as “Narayanan”), Gou et al. (CN 113941029 A, Jan. 18, 2022, machine translation, hereafter as “Gou”), Runge et al. (US 2013/0331869 A1, Dec. 12, 2013, hereafter as “Runge”), Li et al. (“Arthroscopic debridement of the osteoarthritic knee combined with hyaluronic acid (Orthovisc®) treatment: A case series and review of the literature”, J Orthop Surg Res., 2008 Sep 17, 3:43; hereafter as “Li”) and Das et al. (“Laponite-based Nanomaterials for Biomedical Applications: A Review”, Current Pharmaceutical Design, 2019, 25, 424-443; hereafter as “Das”) as evidenced by Sigma Aldrich - PCLF (see PTO-892), Yaszemski et al. (“Reformulating polycaprolactone fumarate to eliminate toxic diethylene glycol: Effects of polymeric branching and autoclave sterilization on material properties”, Acta Biomaterialia, 8 (2012) 133-143; hereafter as “Yaszemski”) and Sigma Aldrich - PLGA (see PTO-892), as applied to claims 1 and 7 above, and further in view of Massaro et al. (“Multifunctional Carrier Based on Halloysite/Laponite Hybrid Hydrogel for Kartogenin Delivery”, ACS Med Chem Lett, 2018 Oct 22:10(4), pp. 419-424; hereafter as “Massaro”).
The claimed invention is described above.
Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Li and Das teach the elements discussed above.
Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Li and Das are silent to “0.05% to 2% w/v of LAP”.
Massaro teaches a method of treating osteoarthritis comprising intraarticular delivery of a LAP-based hydrogel containing kartogenein (abstract). Massaro teaches injecting the hydrogel directly into the affected tissue to reduce systemic side effects and to reduce the frequency of injections (page 419, col 1, para 1). Massaro teaches LAP is a thixotropic hydrogel that can be injected using 21-gauge needles, thus are a convenient platform for delivering tissue-regenerating substances to joints affected by osteoarthritis (page 420, col 1, para 1). Massaro teaches that the aqueous dispersion contains 0.1 wt% (0.1% w/v) of LAP (page 420, Table 1). In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In the instant case, because Massaro’s LAP content of 0.1% w/v overlaps with the instantly claimed two-dimensional silicate nanomaterial content of 0.05-2% w/v, a prima facie case of obviousness exists. See MPEP § 2144.05(I).
The references are all drawn to compositions and devices for the purpose of repairing bone, thus, it would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to include 0.05% to 2% w/v of LAP into the invention of Lerouge/Amodei/Lin/Ritman/Narayanan/Guo/Runge/Li/Das, as suggested by Massaro, with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Massaro teaches the quantity of LAP that is effective for local delivery into the joints of arthritic patients. A skilled artisan would have reasonably expected that inclusion of the claimed amounts of LAP into the invention of Lerouge/Amodei/Lin/Ritman/Narayanan/Guo/Runge/Li/Das would be useful in the treatment of bone disease/disorders.
Thus, the combined teachings of Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Li, Das and Massaro render the instant claim prima facie obvious.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Lerouge et al. (US 2017/0360912 A1, Dec. 21, 2017, hereafter as “Lerouge”) in view of Amodei (US 2011/0172826 A1, Jul. 14, 2011, hereafter as “Amodei”), Lin et al. (WO 2012/118846 A1, Sep. 7, 2012, hereafter as “Lin”), Ritman et al. (US 2010/0221347 A1, Sep. 2, 2010, hereafter as “Ritman”) and Narayanan et al. (“Poly (Lactic Acid)-Based Biomaterials for Orthopaedic Regenerative Engineering”, Adv Drug Deliv Rev. 2016 December 15; Volume 107, pp. 1–76; hereafter as “Narayanan”), Gou et al. (CN 113941029 A, Jan. 18, 2022, machine translation, hereafter as “Gou”), Runge et al. (US 2013/0331869 A1, Dec. 12, 2013, hereafter as “Runge”) and Li et al. (“Arthroscopic debridement of the osteoarthritic knee combined with hyaluronic acid (Orthovisc®) treatment: A case series and review of the literature”, J Orthop Surg Res., 2008 Sep 17, 3:43; hereafter as “Li”) as evidenced by Sigma Aldrich - PCLF (see PTO-892), Yaszemski et al. (“Reformulating polycaprolactone fumarate to eliminate toxic diethylene glycol: Effects of polymeric branching and autoclave sterilization on material properties”, Acta Biomaterialia, 8 (2012) 133-143; hereafter as “Yaszemski”) and Sigma Aldrich - PLGA (see PTO-892), as applied to claim 1 above, and further in view of Li (CN 104706447 A, machine translation, Jun. 17, 2015, hereafter as “CN ‘447”).
The claimed invention is described above.
Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge and Li teach the elements discussed above including varying pore sizes.
Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge and Li are silent to the particular pore size range of 200-800 microns.
CN ‘447 teaches that the average pore size and porosity of the lumbar cancellous bone trabecular bone and the trabecular bone structure were calculated, and the average pore diameter (400-600 microns) and void ratio (70%) of the lumbar vertebrae trabeculae were obtained ([0041]). The information obtained was then used to design the pore structure of the bone cage in order to induce bone ingrowth and achieve the effect of increasing the rate of spinal fusion [0003], [0030] and [0045]).
The references are all drawn to compositions and devices for the purpose of repairing bone, thus, it would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to include a pore size range of 400-600 microns into the bone cage of Lerouge/Amodei/Lin/Ritman/Narayanan/Guo/Runge/Li, as suggested by CN’447, with a reasonable expectation of success. A skilled artisan would have been motivated to do so because CN ‘447 teaches that said pore size range is effective in inducing bone ingrowth.
Thus, the combined teachings of Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Li and CN ‘447 render the instant claims prima facie obvious.
Claims 6 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Lerouge et al. (US 2017/0360912 A1, Dec. 21, 2017, hereafter as “Lerouge”) in view of Amodei (US 2011/0172826 A1, Jul. 14, 2011, hereafter as “Amodei”), Lin et al. (WO 2012/118846 A1, Sep. 7, 2012, hereafter as “Lin”), Ritman et al. (US 2010/0221347 A1, Sep. 2, 2010, hereafter as “Ritman”), Narayanan et al. (“Poly (Lactic Acid)-Based Biomaterials for Orthopaedic Regenerative Engineering”, Adv Drug Deliv Rev. 2016 December 15; Volume 107, pp. 1–76; hereafter as “Narayanan”), Gou et al. (CN 113941029 A, Jan. 18, 2022, machine translation, hereafter as “Gou”), Runge et al. (US 2013/0331869 A1, Dec. 12, 2013, hereafter as “Runge”), Li et al. (“Arthroscopic debridement of the osteoarthritic knee combined with hyaluronic acid (Orthovisc®) treatment: A case series and review of the literature”, J Orthop Surg Res., 2008 Sep 17, 3:43; hereafter as “Li”), Das et al. (“Laponite-based Nanomaterials for Biomedical Applications: A Review”, Current Pharmaceutical Design, 2019, 25, 424-443; hereafter as “Das”) as evidenced by Sigma Aldrich - PCLF (see PTO-892), Yaszemski et al. (“Reformulating polycaprolactone fumarate to eliminate toxic diethylene glycol: Effects of polymeric branching and autoclave sterilization on material properties”, Acta Biomaterialia, 8 (2012) 133-143; hereafter as “Yaszemski”) and Sigma Aldrich - PLGA (see PTO-892), as applied to claims 1 and 6 above, and further in view Jayasuriya et al. (US 2021/0023240 A1, Jan. 28, 2021, hereafter as “Jayasuriya”).
The claimed invention is described above.
Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Li and Daso teach the elements discussed above. Lerouge further teaches the inclusion of chondroitin sulfate (CS) in an amount of 0.5% and 1% is effective in optimizing biological properties such as cell viability and growth ([0355]-[0356]).
Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Li and Das are silent to 5% to 20% w/v of MC.
Jayasuriya teaches compositions comprising a thermoresponsive hydrogel for the purpose of bone repair (abstract; [0004]). Jayasuriya teaches the particular thermoresponsive hydrogel, methylcellulose and can be used in combination with chitosan ([0005]). Jayasuriya teaches that the polymer is present in the thermoresponsive hydrogel at a concentration ranging from about 2% by weight to about 10% by weight ([0011]).
The references are all drawn to compositions and devices for the purpose of repairing bone, thus, it would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to include 1% w/v of CS and 2% to 10% w/v of MC into the invention of Lerouge/Amodei/Lin/Ritman/Narayanan/Guo/Runge/Li/Das, as suggested by Lerouge and Jayasuriya, with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Lerouge teaches that 1% CS improves cell viability and growth and Jayasuriya teaches about 2% to about 20% MC is a suitable amount of thermoresponsive hydrogel in a composition useful in locally delivered bone repair therapy. It would have further been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to optimize the amount of MC by way of routine experimentation with a reasonable expectation of success. MPEP 2144.05(II)(A) 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."
A skilled artisan would have been motivated to do so because Jayasuriya teaches the general conditions of the claim and it is the normal desire of scientists and artisans to improve upon what is already generally known and determine where in a disclosed range is the optimum or workable ranges.
Thus, the combined teachings of Lerouge, Amodei, Lin, Ritman, Narayanan, Guo, Runge, Li, Das and Jayasuriya render the instant claim prima facie obvious.
Response to Arguments
Applicant's arguments, filed 8/4/2026, have been fully considered but they are not persuasive.
Applicant argues that because none of the references teach or suggest “the 3D printed bone graft containment device… comprises a resin comprising from 20 to 50 % by weight caprolactone fumarate combined with 50 to 80 % by weight poly (glycolic acid) or poly lactic-glycolic acid” as recited in claim 1, the rejections should be withdrawn. Remarks, pages 4-7.
In response, it is respectfully submitted that the new limitations have been considered and are addressed in the new rejections above. Applicant’s attention is directed to the following relevant teachings:
Lin which teaches a cage for facilitating fusion of bones, such as vertebrae, or fusion of adjacent bone surfaces, wherein the cage comprises a biodegradable polymeric material, an osteoconductive mineral coating and a bioactive agent (abstract). Lin teaches the particular biodegradable polymers, polycaprolactone, polylactide, polyglycolide, poly(lactide-glycolide), poly(propylene fumarate), poly(caprolactone fumarate), polyethylene glycol, poly(glycolide-co-caprolactone) as well as mixtures and combinations thereof ([0049] and [0067]; claim 17). Lin also teaches that cage fabrication can occur via various methods including Fused Deposition Modeling (FDM) which is a known 3D printing method ([0076]-[0077]). PCLF comprises bio-compatible poly(caprolactone) units which provide flexibility and fumarate repeat units provide cross linking ability without adding any toxic cross-linkers as evidenced by Sigma Aldrich – PCLF. PCLF is also known to be more slowly degradable than over polyesters as evidenced by Yaszemski (page 142; right col., 1st para.). PLGA can be tuned by varying the ratio of lactide to glycolide monomers in order to obtain different degrees of crystallinity, thermal transitions, solubility, and rates of degradation as evidenced by Sigma Aldrich – PCLF.
Ritman which teaches materials and methods related to tissue scaffolds for use in replacing or augmenting various tissues in the body, wherein said tissues include bone (abstract; [0065]). In a particular embodiment, Rittman teaches a scaffolding material comprising polypropylene fumarate (PPF) and polycaprolactone fumarate (PCF) that can be crosslinked and its mechanical properties can be efficiently modulated by varying the composition of PPF in PPF/PCLF blends ([0074]-[0077]).
Narayanan which teaches methods of fabricating scaffolds for tissue regeneration including polylactic acid (PLA)-based structures by a 3D printing process that exhibited excellent structural integrity with superior thermo-mechanical characteristics which was achieved by cross-linking the extruded PLA structures (paragraph bridging pages 6-7). Narayanan also teaches such structures can be utilized for orthopedic applications including the vertebra (page 3, 3rd paragraph; paragraph bridging pages 6-7). Narayanan also teaches that PLA-based materials include PLLA and PLGA (page 2, last para. – page 3, 2nd para.).
The references are all drawn to compositions and devices for the purpose of repairing bone, thus, it would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to include the particular combination of polymers, poly(caprolactone fumarate) and poly(lactide-glycolide) into the bone cage of Amodei as suggested by Lin with a reasonable expectation of success. A skilled artisan would have been motivated to do so because Lin teaches that said polymers are suitable bone cage materials for treating bone and combining equivalents known for the same purpose is prima facie obvious (MPEP 2144.06). It would have also been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to optimize the concentrations of each polymer and arrive at the claimed amounts by way of routine experimentation with a reasonable expectation of success because Lin teaches a finite number of polymers to include PCLF and PLGA as well as polymer mixtures are suitable and PCLF and PLGA are each known to have particular properties wherein modifying the amounts of PCLF and PLGA will effectively alter the properties of the combination (i.e., crosslinkable, flexibility, degradability, solubility, etc.) and allow for tunability depending on the desired properties of said combination. It is the normal desire of scientists or artisans to improve upon what is already generally known including determining the optimum combination of percentages (MPEP 2144.05). It would have further been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to 3D print and cross-link said polymers as suggested by Lin/Ritman/Narayanan with a reasonable expectation of success. A skilled artisan would have been motivated to do so because the prior art teaches that such processes of crosslinking and 3D printing are suitable for said materials in the fabricating of devices in orthopedic applications and because cross-linking, more specifically, improves the mechanical properties of said polymeric materials.
Thus, for these reasons, Applicant' s arguments are found unpersuasive. Said rejection is maintained.
Conclusion
All claims have been rejected; no claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Correspondence
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Casey S. Hagopian
Examiner, Art Unit 1617
/CARLOS A AZPURU/Primary Examiner, Art Unit 1617
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