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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 1/13/2026 has been entered. Claims 1-8, 11-13, and 15-22 are currently pending in this application.
Response to Arguments
Applicant's arguments filed 1/13/2026 have been fully considered but they are not persuasive.
With regard to applicant’s argument on page 6 that Kusanagi does not teach that enzymes are added, but rather present in vivo, the examiner disagrees. Paragraph 0142 clearly discloses that the acellular matrix implant may additionally incorporate enzymes, such as MMPs, which may enhance activation of mature, metabolically active chondrocytes present in the surrounding area host cartilage and migration of these chondrocytes from the native host cartilage into said acellular matrix implant within the lesion. Paragraph 0143, lines 11-22, goes on to say that for the repair of lesions in older subjects, the enzymes (MMPs) are added into the matrix before implantation or they may be used to coat the matrix to promote degradation of the injured cell(s), while in younger patients, these enzymes are naturally present in sufficient amounts.
With regard to applicant’s argument on page 6 that the enzymes of Kusanagi do not directly degrade the barrier composition, the examiner disagrees. First, it is noted that the claims do not recite the term “directly”, nor is support found in applicant’s specification for this term with regard to degradation of the barrier composition. Second, the examiner maintains that the process of promoting degradation of the injured cells via the enzymes (paragraph 0143), coupled with activating chondrocytes from the surrounding native cartilage, via the enzymes, to promote growth of the extracellular matrix and generate a new hyaline cartilage in situ (paragraph 0143), results in full degradation and complete replacement of the implant, including the barrier composition (paragraph 0145). Therefore, the enzyme(s) of Kusanagi are construed to be polymer degrading enzyme(s) since they clearly contribute to the degradation of the polymer barrier composition, as claimed. See rejection below for further explanation.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1, line 8, recites “said enzyme”, which appears to be referring to – said polymer degrading enzyme –, as recited earlier in the claim. Appropriate correction is required.
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.
Claim(s) 1-8, 11-13, 15-18, 20, 21, and 22 is/are rejected under 35 U.S.C. 103 as being unpatentable over US Patent Application Publication No. 2005/0043814 A1 to Kusanagi et al. (Kusanagi).
Regarding at least claim 1
Kusanagi teaches acellular matrix implants for implantation into an articular cartilage or osteochondral lesion and a method for fabrication thereof (abstract).
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Kusanagi meets the limitations of a method for treating a defect in articular cartilage (abstract discloses implantation into an articular cartilage or osteochondral lesion), said method comprising: a) preparing a matrix implant (paragraph 0138 discloses preparation of an acellular matrix implant); b) applying a barrier composition (paragraph 0109 teaches that the barrier composition/first bottom layer function is to protect the integrity of the lesion from cell migration and from effects of various blood and tissue debris and metabolites and also to form a bottom of the cavity into which the implant is deposited; paragraph 0236 teaches that the barrier prevents entry and blocks the migration of subchondral and synovial cells of extraneous components, such as blood-borne agents, cell and cell debris, etc.) comprising a polymer (paragraph 0052 discloses a barrier composition that is made up of a first layer/bottom polymer deposited at the bottom of the lesion) and a polymer degrading enzyme that degrades the barrier composition after application to the bottom of the cartilage defect (paragraph 0142 discloses that the matrix implant may additionally incorporate matrix remodeling enzymes, for the purpose of enhancing activation of mature chondrocytes present in the surrounding native host cartilage and migration of these chondrocytes from the native host cartilage surrounding the lesion cavity into said acellular matrix implant emplaced within said lesion, which promotes growth of the acellular matrix implant and generates a new hyaline cartilage in situ; paragraph 0145 teaches that the result of this process is full degradation of the implant, which includes bottom and top polymer barriers, that occurs after the implant is applied to the bottom of the cartilage defect, as claimed) and c) implanting said matrix implant above the applied barrier composition such that the barrier composition is applied to the bottom of the cartilage defect (paragraph 0052 discloses that the acellular matrix implant is deposited over/above the protective biodegradable polymer barrier deposited at the bottom of the lesion).
However, Kusanagi does not explicitly teach that about 90% of the barrier composition degrades within 14 days after application or wherein about 90% of the barrier composition is degraded within 14 days of applying said barrier composition.
Kusanagi further teaches that the barrier is fully (i.e., 100%) biodegradable and removed naturally from the site of the lesion within time of approximately 2-3 months following the surgery (paragraph 0112), for the purpose of permitting the implant to function for the certain period of time needed for formation of hyaline cartilage such that the sealant is removed metabolically from the healed lesion and replaced with hyaline cartilage (paragraphs 0040 and 0141). Kusanagi also teaches that the process for complete replacement of the implant matrix with the hyaline cartilage typically takes from one week to several months provided that the treated individual becomes normally physically active subjecting said new cartilage to the intermittent hydrostatic pressure by, for example, walking, running, or biking (paragraph 0144).
There is no evidence of record that establishes that changing the degradation rate of the barrier composition such that about 90% of the barrier composition degrades within 14 days would result in a difference in function of the Kusanagi device. Further, a person having ordinary skill in the art, being faced with modifying the degradation rate of the barrier composition, would have a reasonable expectation of success in making such a modification and it appears the device would function as intended being given the claimed degradation rate of the barrier composition. Lastly, applicant has not disclosed that the claimed range solves any stated problem, indicating that 90% of the barrier composition degrades in 14 days “in some embodiments”, and offering other acceptable ranges (e.g., 8 weeks, specification at para. [0012]) and therefore there appears to be no criticality placed on the range as claimed such that it produces an unexpected result.
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to modify the matrix implant of Kusanagi, which is fully degraded within 2-3 months (i.e., 8-12 weeks), such that about 90% of the barrier composition degrades within 14 days after application and wherein about 90% of the barrier composition is degraded within 14 days of applying said barrier composition to the bottom of the cartilage defect, as an obvious matter of design choice within the skill of the art, depending on the desired degradation rate for the individual application, in order to allow the implant to function for the certain period of time needed for formation of hyaline cartilage, which may take from one week to several months, as taught by Kusanagi.
Regarding at least claim 2
Kusanagi teaches the method of claim 1, wherein the barrier composition is applied to subchondral bone (fig. 1A shows the protective polymer barrier applied to subchondral bone).
Regarding at least claim 3
Kusanagi teaches the method of claim 1, wherein the barrier composition is effective to block migration of cells, blood, or other material from the subchondral bone into the cartilage lesion (paragraph 0236 discloses blocking the migration of subchondral and synovial cells of the extraneous components).
Regarding at least claim 4
Kusanagi teaches the method of claim 1, wherein the matrix implant is an acellular matrix implant (at least paragraph 0135).
Regarding at least claim 5
Kusanagi teaches the method of claim 4, wherein the acellular matrix implant comprises one or more of a Type I collagen, a Type II collagen, a Type IV collagen, a collagen containing proteoglycan, a collagen containing glycosaminoglycan, a collagen containing glycoprotein, a polymer of an aromatic organic acid, gelatin, agarose, hyaluronan, fibronectin, laminin, a bioactive peptide growth factor, a cytokine, elastin, fibrin, a polymer made of polylactic acid, a polymer made of polyglycolic acid, poly(epsilon-caprolactone), a polyamino acid, a polypeptide gel, and a polymeric thermo-reversible gelling hydrogel (TRGH) (paragraph 0157 discloses materials that the implant is prepared from, including, for example, Type I collagen).
Regarding at least claim 6
Kusanagi teaches the method of claim 1, wherein said barrier composition comprises one or more of gelatin, Type I collagen, periodate-oxidized gelatin, photo-polymerizable polyethylene glycol-co-poly(a-hydroxy acid) diacrylate macromer, 4-armed polyethylene glycols derivatized with N-(acyloxy)succinimide and thiol plus methylated collagen, derivatized polyethylene glycol (PEG) cross-linked with alkylated collagen, tetra-N- hydroxysuccinimidyl, or tetra-thiol derivatized PEG, and cross-linked PEG with methylated collagen (paragraph 0255 discloses at least tetra-thiol derivatized PEG).
Regarding at least claim 7
Kusanagi teaches the method of claim 1, wherein said barrier composition comprises a second sealant (the top polymer/second layer disclosed in paragraph 0052 meets the limitation of a second sealant as claimed).
Regarding at least claim 8
Kusanagi teaches the method of claim 7, wherein the first or second sealant forms a hydrogel after the barrier composition is applied to the subchondral bone (paragraph 0281 discloses polymerization of the barrier after being applied over the bottom of the lesion).
Regarding at least claim 11
Kusanagi teaches the method of claim 1, wherein the polymer is gelatin or fibrin (paragraph 0216 discloses adding a bone-inducing composition to the protective biodegradable polymer and paragraph 0229 discloses that the bone-inducing composition may be a hydrogel), and wherein the barrier composition comprises thrombin or a crosslinking agent (paragraph 0256 discloses cross-linking reactions beginning upon mixing the three components of the polymers of the barrier; as best understood by the examiner, a crosslinking is therefore present).
Regarding at least claim 12
Kusanagi teaches the method of claim 1, wherein the barrier composition comprises a component that modulates viscosity (paragraph 0091 discloses that the implant is a thermo-reversible gelation hydrogel that has a compound changing physical properties such as viscosity and consistency depending on the temperature; it is construed by the examiner that the barrier composition comprises this compound since the implant is integral with the barrier composition when implanted).
Regarding at least claim 13
Kusanagi teaches the method of claim 1, wherein the barrier composition comprises a stabilizer (paragraph 0163 discloses that the implant must be stabilized and therefore comprise a stabilizer).
Regarding at least claim 15
Kusanagi teaches the method of claim 1, wherein the barrier composition comprises a structural material (the bone-inducing composition added to the barrier composition is a structural material since it provides a supporting matrix as disclosed in paragraph 0232).
Regarding at least claim 16
Kusanagi teaches the method of claim 15, wherein the structural material comprises one or more of a fiber, fibrin, alginate, hyaluronic acid, gelatin, cellulose, or collagen (paragraph 0229 discloses that the bone-inducing composition may be administered as a gel or hydrogel).
Regarding at least claim 17
Kusanagi teaches the method of claim 1, further comprising introducing a protective biodegradable polymer above the matrix implant (paragraph 0235 discloses that the implant is implanted into a lesion between a top protective biodegradable polymer barrier and a bottom protective biodegradable polymer barrier).
Regarding at least claim 18
Kusanagi teaches the method of claim 1, wherein said matrix implant comprises at least one therapeutic agent (at least paragraph 0026 discloses including bone-inducing agents which are therapeutic since they support or promote bone growth and repair of bone defects as disclosed in paragraph 0088).
Regarding at least claim 20
Kusanagi teaches the method of claim 1. Kusanagi also teaches wherein said matrix implant comprises a synovial fluid (paragraph 0340 discloses that new hyaline cartilage is formed and integrated into the native surrounding host cartilage following implantation of the matrix implant in the lesion, resulting in a fully functional cartilage covered with a superficial cartilage layer which eventually grows into or provides the same type of surface as a synovial membrane of the intact joint –the matrix of the integrated implant therefore comprises synovial fluid which is present in the synovial membrane disclosed by Kusanagi).
Regarding at least claim 21
Kusanagi teaches the method of claim 1. Kusanagi also teaches wherein said matrix implant comprises articular chondrocytes (paragraph 0078 discloses the matrix being suitable for receiving activated migrating chondrocytes and osteocytes that provides a structural support for growth and three-dimensional propagation of chondrocytes and for formulating of new hyaline cartilage or for migration of osteochondrocytes into the bone lesions).
Regarding at least claim 22
Kusanagi teaches the method of claim 1, wherein said polymer comprises gelatin, polyethylene glycol (PEG), a derivatized PEG, a cyanoacrylate, a polyurethane, a poly(methylidene malonate), a derivatized polyvinyl alcohol, an acrylic polymer, fibrin, gelatin, polystyrene with catechol side chains, a polyester, a polymer secreted by Phragmatopoma californica, a copolymer of polyethylene glycol and polylactide, a copolymer of polyethylene glycol and polyglycolide, a polyether, a polysaccharide, an oxidized polysaccharide, a polycation polyamine, a polyanion, a poly(ester urea), a copolymer of polyethylene glycol and poly-lactide or poly-glycolide, 4-armed pentaerythritol thiol and a polyethylene glycol diacrylate, 4-armed tetra-N-hydroxysuccinimidyl ester or a tetra-thiol derivatized PEG, a polymer formed from gelatin and oxidized starch, a polymer formed from photo-polymerizable polyethylene glycol-co- poly(a-hydroxy acid) diacrylate macromers, periodate-oxidized gelatin, serum albumin and di- functional polyethylene glycol derivatized with maleimidyl, succinimidyl, phthalimidyl and related active groups, 4-armed polyethylene glycols derivatized with succinimidyl ester and thiol, methylated collagen, or a combination thereof (paragraph 0253 discloses that the polymer comprises at least one of the claimed polymers, i.e., methylated collagen and/or derivatized polyethylene glycol).
Claim(s) 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kusanagi, as applied to claim 18 above, in view of US Patent Application Publication No. 2003/0004578 A1 to Brown et al. (Brown).
Kusanagi teaches the method of claim 18 as explained above. Kusanagi also teaches including bone-inducing agents which are therapeutic since they support or promote bone growth and repair of bone defects (paragraph 0088). However, Kusanagi does not explicitly teach wherein said therapeutic agent comprises an anti-infective agent, a pain medication, an analgesic, an anti-inflammatory agent, an immunosuppressive agent, or a combination thereof.
Brown teaches a composite scaffold for the repair and regeneration of tissue (abstract). The implant of Brown may contain therapeutic agents, such as anti-infectives such as antibiotics and antiviral agents; chemotherapeutic agents (i.e. anticancer agents); anti-rejection agents; analgesics and analgesic combinations; anti-inflammatory agents; hormones such as steroids; growth factors (bone morphogenic proteins (i.e. BMPs 1-7), bone morphogenic-like proteins (i.e. GFD-5, GFD-7 and GFD-8), epidermal growth factor (EGF), fibroblast growth factor (i.e. FGF 1-9), platelet derived growth factor (PDGF), insulin like growth factor (IGF-I and IGF-II), transforming growth factors (i.e. TGF-.beta.I-III), vascular endothelial growth factor (VEGF)); and other naturally derived or genetically engineered proteins, polysaccharides, glycoproteins, or lipoproteins (paragraph 0057), for the purpose of inducing bone growth or releasing medicament (abstract).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention to specify that the therapeutic agent of Kusanagi, which is used to support or promote bone growth and repair bone defects, comprises an anti-infective agent, a pain medication, an analgesic, an anti-inflammatory agent, an immunosuppressive agent, or a combination thereof, in order to induce ingrowth or to release a medicament, as taught by Brown.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA A HOBAN whose telephone number is (571)270-5785. The examiner can normally be reached Monday-Friday 8:00AM-5:00PM.
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/M.A.H/Examiner, Art Unit 3774
/SARAH W ALEMAN/Primary Examiner, Art Unit 3774