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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 05/06/2026 has been entered.
Withdrawal of Rejections
The response and amendments filed on 04/22/2026 are acknowledged. Any previously applied minor objections and/or minor rejections (i.e., formal matters), not explicitly restated here for brevity, have been withdrawn necessitated by Applicant’s formality correction and/or amendments. For the purposes of clarity of the record, the reasons for the Examiner’s withdrawal, and/or maintaining, if applicable, of the substantive or essential claim rejections are detailed directly below and/or in the Examiner’s Response to Arguments section.
Briefly, the previous claim rejections under 35 U.S.C. 103 for obviousness have been withdrawn necessitated by Applicant’s amendments; however, new grounds of rejection are set forth below.
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, Obviousness
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 5-7 and 15-18 are rejected under 35 U.S.C. 103 as being unpatentable over Detamore (US 2016/0235892; Date of Publication: August 18, 2016 – previously cited) in view of Deng (Injectable in situ cross-linking hyaluronic acid/carboxymethylcellulose based hydrogels for drug release; 2018 – newly cited) and Stragies (WO 2019/197608; Date of Publication: October 17, 2019 – newly cited).
Detamore’s general disclosure relates to compositions comprising decellularized cartilage tissues powders for treating osteochondral defects (see, e.g., Detamore, abstract). Moreover, Detamore discloses that the cartilage tissue powder can be used for “treating full and partial-thickness cartilage defects caused by traumatic injury and osteoarthritis. This cartilage or bone tissue powder could also be used in tendon, ligament, meniscus, and TMJ regenerative applications. Preferably, the decellularized cartilage (DCC) fragment or powder is a chondroinductive material, meaning that it induces chondrogenesis” (see, e.g., Detamore, [0006]).
Regarding claim 5 pertaining to the micronized cartilage powder, Detamore teaches a decellularized cartilage tissue powder in the form of a paste, putty, hydrogel, and scaffold (see, e.g., Detamore, abstract). Detamore teaches a composition comprising the micronized cartilage powder particulates ranging from between about 10 w/v % and about 90 w/v % (see, e.g., Detamore, [0012]). Additionally, Detamore teaches making a gel comprising 15% w/v of solubilized cartilage particulates (see, e.g., Detamore, [0119]). One of ordinary skill in the art would readily understand that 10 w/v % and about 90 w/v %, as taught by Detamore, can correlate to 10 to 90 parts by weight, which overlaps with the instantly claimed invention.
Regarding claim 6 pertaining to the particle diameter for the micronized cartilage powder, Detamore teaches a decellularized cartilage tissue powder, wherein the powder particulates range in size from about 1 nm to about 500 µm (see, e.g., Detamore, [0007]). The claimed range of the powder diameter overlaps with the teachings of Detamore; therefore, a prima facie case of obviousness exists (see, e.g., MPEP 2144.05(I)).
Regarding claim 7 pertaining to the micronized cartilage powder, Detamore teaches that the cartilage powder contains at least 85% glycosaminoglycans (see, e.g., Detamore, [0009]). Moreover, Detamore teaches that “Collagen, glycosaminoglycans (GAGs), and ECM-based matrices are the main categories of “raw materials” found naturally in the body that can be incorporated into scaffolds” (see, e.g., Detamore, [0006]). Moreover, collagen inherently comprises up to 60% of the dry weight of cartilage (see, e.g., Fox – Art of Record).
Regarding claims 15-18, these are product-by-process claims; therefore, patentability is based on the product itself, namely the micronized cartilage powder composition recited in claim 5 (see, e.g., MPEP 2113(I)). The process steps recited in claims 15-18 result in a decellularized, micronized cartilage powder, which is taught by Detamore (see, e.g., Detamore, abstract & [0007]).
However, Detamore does not teach: wherein the hyaluronic acid and carboxymethylcellulose are crosslinked by a crosslinking agent (claim 5); or wherein the crosslinking agent is BDDE (claim 5); or wherein the crosslinked product of hyaluronic acid and carboxymethylcellulose is in an amount of 50 to 80 parts by weight relative to the total weight of the composition (claim 5).
Deng’s general disclosure relates to “A series of injectable in situ cross-linking hyaluronic acid/carboxymethylcellulose based hydrogels (HA/CMC) was prepared via disulfide bonds by the oxidation of dissolved oxygen. The results showed that HA/CMC hydrogels exhibited tunable gelling time, appropriate rheology properties, high swelling ratio, good stability, and sustained drug release ability” (see, e.g., Deng, abstract). Moreover, Deng discloses “The results showed that the series of injectable HA/CMC hydrogels exhibited good comprehensive performance, signifying that HA/CMC hydrogels could be potentially used in the fields of short- and medium-term controlled drug release, cell encapsulation, regenerative medicine, and tissue engineering” (see, e.g., Deng, Introduction, pg. 1645).
Regarding claim 5 pertaining to a crosslinked product of hyaluronic acid and carboxymethylcellulose, Deng teaches cross-linking hyaluronic acid/carboxymethyl
cellulose based hydrogels (see, e.g., Deng, abstract & Methods – Sections 2.3-2.7). Furthermore, Deng teaches “A concentration of 1, 2, and 3% (w/v) of HA-SH solutions were mixed with equivalent volume of different concentration of CMC-SH solutions (1, 2, and 3% (w/v)) to prepare HA1/CMC1, HA2/CMC2, and HA3/CMC3 hydrogels at 37 °C, respectively” (see, e.g., Deng, Section 2.3, pg. 1646). One of ordinary skill in the art would readily recognize that one can produce a composition wherein the crosslinked hyaluronic acid and carboxymethylcellulose is 50 to 80 parts by weight, wherein the concentration of hyaluronic acid and carboxymethylcellulose is 1, 2, and 3% (w/v), as taught by Deng.
Stragies’ general disclosure relates to “a dermal filler composition based on crosslinked hyaluronic acid, calcium phosphate material particles and carboxymethyl cellulose” (see, e.g., Stragies, [0001]). Moreover, Stragies discloses “the unexpected finding that crosslinked hyaluronic acid (HA) in combination with carboxymethyl cellulose (CMC) enables the provision of a dermal filler composition in which calcium hydroxyapatite (CaHA) particles are stably suspended over time without undergoing phase separation, despite the composition’s desirable low viscosity and extrusion force. The crosslinked HA provides a stronger rheological profile as compared to conventionally used non- crosslinked CMC at similar concentration and has a long in vivo persistence of up to 24 months. Overall, the dermal filler composition of the present invention provides an optimal balance of volumizing capacity, longevity and ease of injection” (see, e.g., Stragies, [0018]).
Regarding claim 5 pertaining to the crosslinking agent, Stragies teaches that the crosslinking agent for preparing crosslinked hyaluronic acid and carboxymethylcellulose is 1,4-butanediol diglycidyl ether (BDDE) (see, e.g., Stragies, [0012]).
It would have been first obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine Detamore’s micronized cartilage powder composition with Deng’s crosslinked hyaluronic acid and carboxymethylcellulose composition. One would have been motivated to do so because Deng teaches “All HA/CMC hydrogels exhibited good comprehensive performance, such as suitable gelling time, porous network structure, good rheology properties, high swelling ratio, favorable stability, and appropriate in vitro sustained release ability (using BSA as drug model), and the performance of hydrogels
was related to the concentration of precursor solution. The series of injectable HA/CMC
hydrogels could be potentially used in the biomedical fields, such as controlled drug release,
cell encapsulation, regenerative medicine, and tissue engineering” (see, e.g., Deng, Conclusions, pg. 1653). Moreover, Detamore teaches “The present invention provides decellularized cartilage (DCC) fragments or powder as a raw material component to be utilized for scaffolds, such that it provides a microenvironment similar to that of native cartilage tissue. The decellularized cartilage powder described herein provides a platform technology upon which many cartilage, or even bone, tissue engineering scaffolds could be based on. It revolutionizes the field of treating full and partial-thickness cartilage defects caused by traumatic injury and osteoarthritis. This cartilage or bone tissue powder could also be used in tendon, ligament, meniscus, and TMJ regenerative applications. Preferably, the decellularized cartilage (DCC) fragment or powder is a chondroinductive material, meaning that it induces chondrogenesis” (see, e.g., Detamore, [0006]). Therefore, based on the teachings of Detamore and Deng, it would have been obvious to combine a micronized cartilage product with a composition comprising hyaluronic acid and carboxymethylcellulose because this would produce a composition for delivery and controlled release of the micronized cartilage powder for cartilage regeneration. One would have expected success because Detamore and Deng both teach hydrogel compositions for drug delivery.
It would have been secondly obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce Detamore’s micronized cartilage powder composition in combination with Deng’s crosslinked hyaluronic acid and carboxymethylcellulose composition, wherein the hyaluronic acid and carboxymethylcellulose are crosslinked using 1,4-butanediol diglycidyl ether (BDDE), as taught by Stragies. One would have been motivated to do so because Stragies teaches that BDDE can be used to crosslink hyaluronic acid in combination with carboxymethylcellulose (see, e.g., Stragies, [0011]-[0012]). Moreover, Detamore teaches producing a hydrogel cartilage composition through a water-soluble cross-linked network of polymer chains (see, e.g., Detamore, [0011]), and Deng teaches crosslinking of hyaluronic acid and carboxymethylcellulose to produce hydrogels because these crosslinked hydrogels “exhibited good comprehensive performance, such as suitable gelling time, porous network structure, good rheology properties, high swelling ratio, favorable stability, and appropriate in vitro sustained release ability (see, e.g., Deng, Conclusions, pg. 1653). Therefore, based on the teachings of Detamore, Deng, and Stragies, it would have been obvious to crosslink hyaluronic acid and carboxymethylcellulose with BDDE. One would have expected success because Detamore, Deng, and Stragies all teach pharmaceutical or medical treatments and/or crosslinked compositions.
Regarding claim 5 pertaining to the complex viscosity, this limitation is considered inherent (see, e.g., MPEP 2112(III)). The combined prior art of Detamore, Deng, and Stragies teaches the instantly claimed composition; therefore, this composition would result in a complex viscosity of 35,000 to 45,000 Pa
∙
s. Therefore, the combined prior art of Detamore, Deng, and Stragies, as discussed above, renders obvious the complex viscosity limitation recited in claim 5.
Regarding claim 5’s limitations pertaining to the weights of the micronized cartilage powder and the crosslinked product of hyaluronic acid and carboxymethylcellulose to the total weight of the composition, those working in the biological and/or pharmaceutical arts would understand that the adjustments of particular conventional working conditions (e.g., concentration or amount of a compound) is deemed a matter of judicious selection and routine optimization, which is within the purview of the skilled artisan (see, e.g., MPEP 2144.05). For example, the disclosure of Detamore states that if the “cartilage powder particulates are suspended at a high concentration, the particulates can form a composition that is putty-like, and if suspended at a somewhat lower concentration, it can form a composition that is paste-like” (see, e.g., Detamore, [0012]). Moreover, Detamore teaches a composition comprising cartilage powder particulates ranging from between about 10 w/v % and about 90 w/v % (see, e.g., Detamore, [0012]), and Deng teaches “A concentration of 1, 2, and 3% (w/v) of HA-SH solutions were mixed with equivalent volume of different concentration of CMC-SH solutions (1, 2, and 3% (w/v)) to prepare HA1/CMC1, HA2/CMC2, and HA3/CMC3 hydrogels at 37 °C, respectively” (see, e.g., Deng, Section 2.3, pg. 1646). One of ordinary skill in the art would readily recognize that one can produce a composition wherein the crosslinked biocompatible polymer is 10 to 90 parts by weight of the composition, wherein the concentration of hyaluronic acid and carboxymethylcellulose is 1, 2, and 3% (w/v). Therefore, based on these concentrations and percentages, one of ordinary skill in the art would readily understand how to form a composition comprising micronized cartilage, hyaluronic acid, and carboxymethylcellulose by weight relative to the total weight of the composition. Furthermore, this is motivation for someone of ordinary skill in the art to practice or test the parameter widely to find those that are functional or optimal which then would be inclusive or cover the steps as instantly claimed. Absent any teaching of criticality by the applicant concerning the percentage, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are result effective variables which can be met as a matter of routine optimization.
Regarding claims 7’s limitations pertaining to the percentage and/or weight ratios of the cartilage powder and/or glycosaminoglycans within the composition, those working in the biological and/or pharmaceutical arts would understand that the adjustments of particular conventional working conditions (e.g., concentration or amount of a compound) is deemed a matter of judicious selection and routine optimization, which is within the purview of the skilled artisan (see, e.g., MPEP 2144.05). For example, the disclosure of Detamore states that if the “cartilage powder particulates are suspended at a high concentration, the particulates can form a composition that is putty-like, and if suspended at a somewhat lower concentration, it can form a composition that is paste-like” (see, e.g., Detamore, [0012]). Furthermore, Detamore states that retaining glycosaminoglycans within the powdered cartilage composition is crucial as the size of the micronized cartilage versus the coarse ground cartilage is more ideal to incorporate into 3D scaffolds, such as pastes, hydrogels, and microspheres (see, e.g., Detamore, [0169]). Therefore, one of ordinary skill in the art would reasonably understand that the amount of cartilage powder within the composition influences the viscosity and resulting composition (i.e., putty vs paste). Furthermore, Fox (Art of Record) collagen is inherently present in cartilage and makes up about 60% of the dry weight of cartilage (see, e.g., Fox – Art of Record). This is motivation for someone of ordinary skill in the art to practice or test the parameter widely to find those that are functional or optimal which then would be inclusive or cover the steps as instantly claimed. Absent any teaching of criticality by the applicant concerning the percentage, it would be prima facie obvious that one of ordinary skill in the art would recognize these limitations are result effective variables which can be met as a matter of routine optimization.
Examiner’s Response to Arguments
Regarding Applicant’s arguments that Huang does not teach a crosslinked product of hyaluronic acid and carboxymethylcellulose (remarks, pages 7-9), this argument is moot because Huang was not relied upon in the above presented rejection. Instead, newly presented Deng as set forth above to teach a crosslinked product of hyaluronic acid and carboxymethylcellulose; therefore, Applicant’s arguments pertaining to Huang are moot.
Art of Record
Sophia Fox AJ, Bedi A, Rodeo SA. The basic science of articular cartilage: structure, composition, and function. Sports Health. 2009 Nov;1(6):461-8. doi: 10.1177/1941738109350438. PMID: 23015907; PMCID: PMC3445147.
Conclusion
Claims 5-7 and 15-18 are rejected.
No claims are allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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