DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 07/18/2024, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
Receipt is acknowledged of Applicants’ claimed invention filed on 07/18/2024 in the matter of Application N° 18/730,010. Said documents are entered on the record. The Examiner further acknowledges the following:
Thus, claims 1-12 represent all claims currently under consideration.
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.
Claims 1-12 are rejected under 35 U.S.C. 103 as being unpatentable over Ding et al. (Chitosan/Dextran Hydrogel Constructs Containing Strontium Doped Hydroxyapatite with Enhanced Osteogenic Potential in Rat Cranium), in view of Huang et al. An injectable nano-hydroxyapatite (n-HA)/glycol chitosan (G-CS)/hyaluronic acid (HyA) composite hydrogel for bone tissue engineering, and Biomimetic remineralization of dentin Li-na Niu1, Wei Zhang2, David H. Pashley3, Lorenzo Breschi4, Jing Mao2, Ji-hua Chen1, and Franklin R. Tay3, 5.
Regarding claims 1 and 2, Ding et al. teach nanocomposite scaffolds comprising hydroxypropyl chitosan/aldehyde dextran hydrogel and strontium-substituted nanohydroxyapatite (Sr-nHA) nanoparticles for bone tissue engineering (See Abstract). Ding et al. specifically disclose hydroxyapatite materials wherein strontium metal replaces calcium in the apatite structure. Ding et al. further disclose molar ratios of Sr/(Sr+Ca) at 0%, 50%, and 100% (See Abstract), thereby expressly teaching that the calcium of the apatite may be entirely or partially replaced by metal ions.
Ding et al. additionally teach that incorporation of the strontium-substituted hydroxyapatite enhances cell proliferation, osteogenic differentiation, and bone formation (See Abstract), thereby demonstrating the suitability of the substituted apatite material as a filler or scaffold component in biomaterial applications.
Accordingly, Ding et al. teach an apatite containing metal wherein the metal entirely or partially replaces calcium of the apatite, as recited in claim 1.
To the extent claim 1 is interpreted as requiring use specifically “for a filler,” Ding et al. teach incorporation of the substituted apatite particles into hydrogel scaffold matrices to improve structural and biological properties, which constitutes use of the apatite material as a filler component within a composite material.
It would have been obvious to one of ordinary skill in the art at the time of the invention to utilize the substituted apatite material of Ding et al. as a filler because Ding et al. expressly teach incorporation of the particles into composite scaffold matrices for enhancing mechanical and osteogenic properties. The modification merely represents use of a known substituted apatite material for its established purpose of improving composite material properties and would have yielded predictable results.
Further, substitution of calcium ions in apatite with other metal ions, such as strontium, represents a known technique in the biomaterials art for modifying apatite properties. Ding et al. expressly demonstrate partial and complete replacement of calcium with strontium ions, thereby rendering the claimed subject matter obvious.
Regarding claim 3, as discussed above with respect to claim 1, Ding et al. teach an apatite containing metal wherein the metal entirely or partially replaces calcium of the apatite. Ding et al. specifically disclose strontium substituted nanohydroxyapatite materials having varying Sr/(Sr+Ca) molar ratios, including partial and complete substitution of calcium by strontium (See Abstract).
Ding et al. further disclose characterization and release behavior of Sr and Ca ions using inductively coupled plasma-optical emission spectroscopy (See 2.4.6), thereby evidencing ion substitution and release behavior occurring in solution environments. Ding et al. do not expressly disclose using a laser during the substitution process.
However, it would have been obvious to one of ordinary skill in the art at the time of the invention to utilize a laser or optical energy source during solution-based apatite modification or processing because lasers were well known in the materials processing art for inducing, facilitating, analyzing, or controlling ion exchange, particle modification, crystallization, and solution-phase material processing. Use of a laser merely represents the application of a known energy source and analytical/process control technique to a known apatite substitution process to obtain predictable results.
Further, the use of optical or laser-based processing and analytical techniques in conjunction with ion-substituted apatite systems would have been obvious as a matter of routine optimization of process parameters, including energy input, reaction conditions, and ion substitution efficiency.
The claimed use of a laser would have predictably facilitated monitoring, excitation, or processing of the ion substitution reaction occurring in solution. Applying a known laser technique to a known metal-substituted apatite process amounts to the predictable use of prior art elements according to their established functions.
Regarding claim 4, as discussed above with respect to claims 1 and 3, Ding et al. teach apatite materials wherein metal ions, such as strontium, entirely or partially replace calcium ions in hydroxyapatite structures.
However, Ding et al. do not expressly disclose that the apatite has a quadrangular shape.
However, it would have been obvious to one of ordinary skill in the art at the time of the invention to form the apatite particles in a quadrangular or quadrilateral shape because particle geometry and morphology are recognized result-effective variables in the biomaterials and particle engineering arts. Selection of a particular particle shape would have depended upon desired packing properties, surface area, mechanical reinforcement characteristics, or processing considerations.
Further, varying apatite particle morphology, including angular, polygonal, plate-like, rod-like, or quadrilateral geometries, was well known in the art and would have represented no more than a routine design choice absent a showing of criticality or unexpected results associated specifically with the claimed quadrangular shape.
The claimed quadrangular shape merely constitutes optimization of a known particle characteristic to obtain predictable results relating to composite filler performance and scaffold morphology.
Regarding claim 5, Ding et al. disclose a filler composition comprising apatite particles as recited in the claim. However, Ding et al. do not expressly disclose that the filler composition further comprises hyaluronic acid.
Huang et al. disclose compositions comprising nano-hydroxyapatite and hyaluronic acid and teach that hyaluronic acid is a widely used biodegradable and biocompatible polymeric material suitable for incorporation into hydroxyapatite-containing compositions (See Abstract, and Introduction).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the filler composition of Ding et al. to further comprise hyaluronic acid as taught by Huang et al. Hyaluronic acid was well known in the cosmetic and biomedical arts as a biocompatible material commonly employed in injectable filler formulations due to its favorable tissue compatibility, hydration properties, and ability to provide volume augmentation. One of ordinary skill in the art would have been motivated to incorporate hyaluronic acid into the apatite-containing filler composition of Ding et al. to improve the filler characteristics and tissue compatibility of the composition, with a reasonable expectation of success because both apatite materials and hyaluronic acid were known and compatible components used in injectable biomaterial and filler formulations.
Regarding claim 6, Ding et al. as modified by Huang et al. disclose a filler composition comprising apatite particles and hyaluronic acid as recited in claim 5. However, neither Ding et al. nor Huang et al. expressly disclose that the metal is eluted in the form of ions in vivo.
Huang et al. disclose a nano-hydroxyapatite/glycol chitosan/hyaluronic acid composite hydrogel for bone reconstruction in vivo and teach that the composite hydrogel exhibits biodegradability and biocompatibility in physiological environments (See Introduction). As hydroxyapatite is a calcium phosphate material containing metal ions, it was well understood in the art that biodegradation and resorption of hydroxyapatite-containing materials in vivo result in the release of constituent metal ions, such as calcium ions, into the surrounding biological environment.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention that the metal present in the apatite particles of the filler composition would be eluted in the form of ions in vivo. The release of metal ions from biodegradable apatite materials under physiological conditions was a well-known and inherent property of such materials. One of ordinary skill in the art would have reasonably expected that, upon implantation or injection in vivo, the apatite containing filler composition would undergo gradual degradation or resorption, thereby releasing constituent metal ions into the surrounding tissue.
Regarding claim 7, Ding et al. as modified by Huang et al. disclose a filler composition comprising apatite and hyaluronic acid as recited in claim 6. However, Ding et al. and Huang et al. do not expressly disclose that the filler composition is for oral tissue.
Niu et al. disclose calcium phosphate biomineralization processes involved in hard tissue mineralization and teach that calcium and phosphate ions participate in the formation of mineralized tissues through biomimetic mechanisms. Niu et al. further discuss calcium phosphate materials in the context of biological mineralization and hard tissue formation (See 2.1 Particle-based vs ion-based crystallization).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to utilize the apatite-containing filler composition of Ding et al. as modified by Huang et al. for oral tissue applications in view of the teachings of Niu et al. because apatite and calcium phosphate materials were known to be biocompatible materials associated with mineralized oral tissues and hard tissues regeneration. One of ordinary skill in the art would have reasonably expected such materials to be suitable for oral tissue applications, including augmentation, repair, regeneration, or reconstruction of oral tissues, due to their recognized similarity to naturally occurring mineral components of such tissues.
Accordingly, it would have been obvious to employ the filler composition of claim 6 for oral tissue applications, and claim 7 would therefore have been obvious over Ding et al. in view of Huang et al. and further in view of Niu et al.
Regarding claim 8, Ding et al. disclose apatite compositions comprising ionic substitutions within the hydroxyapatite structure, including Zn2+, Si4+, Mg2+, F-, CO32- , and Sr2+. Ding et al. further teach that such dopants alter the properties of hydroxyapatite, including its solubility, thereby facilitating the release of ions from the apatite structure under physiological conditions (See Introduction, paragraph 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention that ionic-substituted apatite materials, particularly those containing zinc ions, would release ions in vivo as a consequence of their solubility and interaction with physiological fluids. Zinc ions were well known in the art to possess antibacterial activity and to inhibit bacterial growth. Therefore, one of ordinary skill in the art would have reasonably expected the ion-eluting apatite composition of Ding et al. to exhibit antibacterial properties upon release of the incorporated ions in vivo. Accordingly, the filler composition of Ding et al. as modified by Huang et al. and Niu et al., would have inherently or predictably possessed antibacterial properties resulting from the elution of ions in vivo.
Regarding claim 9, Ding et al. disclose apatite compositions comprising ionic substitutions within the hydroxyapatite structure, including Zn2+, Si4+, Mg2+, F-, CO32- , and Sr2+. Ding et al. teach that the substituted ions may be incorporated into the apatite lattice in varying amounts to modify the properties of the apatite material. Ding et al. specifically disclose zinc-substituted hydroxyapatite compositions containing zinc in amounts that overlap with or fall within the claimed range of 0.05 to 20% by weight of the total apatite. Alternatively, it would have been obvious to one of ordinary skill in the art to select a zinc substitution level within the claimed range because such amounts represent routine optimization of a result effective variable used to tailor the biological and physicochemical properties of apatite materials.
Regarding claim 10, Ding et al. as modified by Huang et al. disclose a filler composition comprising apatite and hyaluronic acid as recited in claim 5.
Huang et al. disclose nano-hydroxyapatite/glycol chitosan/hyaluronic acid composite hydrogels comprising 0.5 mg/mL nano-hydroxyapatite, 5 mg/mL glycol chitosan, and 0.5-1.5mg/mL hyaluronic acid aldehydes. These disclosed formulations contain approximately 7.1-8.3 wt.% nano-hydroxyapatite based on the total solids content of the composition, which falls within the claimed range of 1-50 wt.% apatite (See 2.3 Preparation of nano-hydroxyapatite/glycol chitosan/hyaluronic acid composite hydrogel, Table 1).
Therefore, Huang et al. expressly teach an apatite concentration encompassed by the claimed range. It would have been obvious to one of ordinary skill in the art to employ the apatite concentration taught by Huang et al. in the filler composition of Ding et al., with a reasonable expectation of success because Huang et al. demonstrate that such concentrations are suitable for compositions comprising both apatite and hyaluronic acid.
Regarding claim 11, Ding et al. as modified by Huang et al. disclose a filler composition comprising apatite and hyaluronic acid as recited in claim 6.
Ding et al. expressly disclose that a variety of ionic substitutions may be introduced into the hydroxyapatite structure, including Zn2+, Si4+, Mg2+, F-, and CO32- . thus, Ding et al. teach apatite compositions comprising magnesium ions incorporated into the apatite structure (See Introduction, paragraph 5).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention to employ magnesium ions in the apatite component of the filler composition because Ding et al. expressly identify magnesium as a suitable ionic substituent for hydroxyapatite and teach that such substitutions may be used to modify the properties of the apatite material.
Regarding claim 12, Ding et al., Huang et al., and Niu et al., disclose a filler composition comprising magnesium-containing apatite and hyaluronic acid as recited in claim 11.
Huang et al. disclose a nano-hydroxyapatite/glycol chitosan/hyaluronic acid composite hydrogel. Hydrogels are well known to absorb aqueous fluids and undergo swelling when exposed to physiological environments due to the hydrophilic nature of their polymeric networks. Hyaluronic acid, in particular is recognized for its ability to absorb and retain significant amounts of water.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the invention that the hydrogel-based filler composition of Huang et al., comprising hyaluronic acid and apatite, would swell upon contact with body fluids. Such swelling represents an expected and inherent property of hydrophilic hydrogel compositions intended for implantation or tissue-contact applications.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Barber whose telephone number is (703) 756-5302. The examiner can normally be reached on Monday through Friday from 6:30 AM to 3:30 PM EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert A. Wax, can be reached at telephone number (571) 272-0623. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KIMBERLY BARBER/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
Prosecution Insights