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 .
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/30/2026 has been entered. Applicant's Remarks filed 04/02/2026 have been fully considered. Please see response in following sections.
Status of Claims
Claims 1, 12 and 13 are pending and currently under examination.
Priority
This instant application 17/050,752 filed on 10/26/2020 is a 371 of PCT/JP2019/017578 filed on 04/25/2019 and claims benefit of JAPAN 2018-087430 filed on 04/27/2018.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy of foreign Application JAPAN 2018-087430 is filed on 10/26/2020 in Japanese, no English translation is included in the certified copy of foreign Application No JAPAN 2018-087430. Applicant’s right of foreign priority is not perfected due to lack of English translation thereof. The priority date of instant application is determined to be 04/25/2019, the filing date of PCT/JP2019/017578.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
Claims 1, 12 and 13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 recites “A hydroxyapatite comprising Mg, Na, K, and Si, the hydroxyapatite having a crystallite size of 50 Å to 120 Å, the crystallite size determined by X-ray structural analysis, based on a diffraction peak observed in a range of 2θ = 31.5.000º to 32.5000º, wherein the hydroxyapatite is derived from eggshell...”. Claim 1 is construed as hydroxyapatite comprising Mg, Na, K and Si and having a crystallite size of 50 to 120 Å, wherein all the recited minerals Mg, Na, K and Si are required component of the hydroxyapatite.
However, instant specification does not disclose X-ray spectrum/analysis of instantly claimed hydroxyapatite comprising Mg, Na, K and Si. There is only one working example in instant specification(See Experiment 1, page 9), wherein trace elemental analysis was performed by ICP emission spectrometer to support hydroxyapatite comprising Mg, Na, K and Si (See Table 1), but no X-ray spectrum analysis is disclosed for instant Example 1. The Declaration by Koichi Nakamura disclosed X-ray spectrum to support the microcrystalline hydroxyapatite has a crystallite size of 10 to 150 Å. However, the Declaration is directed to “hydroxyapatite comprising Mg” which does not disclose the component of microcrystalline hydroxyapatite as comprising Mg, Na, K and Si. As such, instant claimed hydroxyapatite comprising Mg, Na, K and Si of claim 1 lacks sufficient support for hydroxyapatite having crystallite size of 50 to 120 Å” determined by X-ray structural analysis as claimed at the time instant application was filed.
New claim 12 is directed to hydroxyapatite having specific Ca/Mg atom numbers . Instant specification alleged “the hydroxyapatite according to [1] or [2], represented by the following chemical formula: (Ca:Mg)10(PO4)6(OH)2 , wherein (Ca:Mg)10 denotes that the total number of Ca atoms and Mg atoms equals to 10, with the number of Ca atoms being from 7 to 9, and the number of Mg atoms being from 1 to 3” (Spec, page 2). However, there is no embodiment/working example or experiment data to characterize/confirm the components of hydroxyapatite wherein the number of Ca and Mg atoms are present as recited in claim 12 . Table 1 (Spec, page 9) shows the presence of Mg, Na, K, Si, etc. as expressed in ppm by mass(mg/kg), but no amount of Mg to Ca are disclosed to support “the total number of Ca atoms and Mg atoms equals to 10, with the number of Ca atoms being from 7 to 9, and the number of Mg atoms being from 1 to 3”. In absence of sufficient disclosure of structural characterization(e.g. molecular formula, X-ray pattern, etc.) of instant claimed hydroxyapatite comprising Mg, Na, K and Si, the specification does not clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed.
Response to Arguments
Applicant argues " The Specification explicitly discloses that the claimed hydroxyapatite has a crystallite size in the claimed range (original Specification, page 4, lines 23-25). The Specification also explicitly discloses that the hydroxyapatite further contains at least one of Na, K, and Si (page 6, lines 13-14). It is evident that the crystallite size disclosed in the Specification is applicable to the hydroxyapatite embodiments containing Na, K, and/or Si. The fact that there are no working examples that include both claimed features in the same embodiment does not negate the above. A patent applicant is not required to provide working examples of all embodiments disclosed in a patent application and/or all embodiments claimed. ”(Remarks, page 5-6/11).
RESPONSE: Applicant’s argument is fully considered, but NOT persuasive. Although it’s not required to provide working examples for all embodiments disclosed in a patent application, Applicant is required to provide sufficient working example/evidence to demonstrate possession of the claimed subject matter at the time the application was filed. Instant claim 1 recites “Hydroxyapatite comprising Mg, Na, K, and Si, the hydroxyapatite having a crystallite size determined by X-ray structural analysis….” “The hydroxyapatite” recited in the same claim all refer back to the hydroxyapatite comprising Mg, Na, K, and Si wherein all Mg, Na, K, and Si are components of the hydroxyapatite. As such, claim 1 is construed as a hydroxyapatite comprising Mg, Na, K, and Si, and having a crystallite size of 50 Å to 120 Å. Instant specification is required to provide support for the hydroxyapatite comprising Mg, Na, K, and Si and having a crystallite size of 50 Å to 120 Å determined by X-ray structural analysis as claimed. It’s also required to provide support for the hydroxyapatite with the chemical formula (Ca:Mg)10(PO4)6(OH)2 and having a crystallite size of 50 Å to 120 Å determined by X-ray structural analysis as claimed. Please note X-ray analysis of microcrystalline hydroxyapatite comprising Mg or “contains at least one mineral selected from the claimed group” is not considered the same as for X-ray analysis of hydroxyapatite comprising all components of Mg, Na, K and Si or hydroxyapatite with specific formula as claimed, since different elements at different amount or combination thereof might affect the microcrystalline structure and crystallite of hydroxyapatite.
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.
Claims 1, 12 and 13 are 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.
Independent claims 1 and 12 recite “the hydroxyapatite comprises finely crystallized hydroxyapatite or a mixture of finely crystallized hydroxyapatite with low crystalline hydroxyapatite”. It’ not clear how the hydroxyapatite is categorized and what’s the threshold of crystallite size for finely crystallized hydroxyapatite or low crystalline hydroxyapatite. In addition, instant claims do not specify the relative amount or ratio of finely crystallized hydroxyapatite and low crystalline hydroxyapatite where the hydroxyapatite is a mixture. The lack of clarity renders the claims indefinite since the resulting claims do not clearly set forth the metes and bounds of the patent protection desired.
Claim 13 is rejected due to dependency on claim 1.
Claim Rejections - 35 USC § 102/103
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 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
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, 12 and 13 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Lee et al. (Tissue Engineering and Regenerative Medicine, Vol. 11, No. 2, 2014, pages 113-120, Applicant’s IDS dated 12/08/2023, “Comparative Study of Hydroxyapatite Prepared from Seashells and Eggshells as a Bone Graft Material”).
Lee teaches hydroxyapatite made from natural source of calcium oxide (CaO) that is obtained by calcination of eggshell (eHA) and seashells (sHA) as a bone graft material (See abstract, Materials and Methods on page 114). Lee teaches the physical and structural property of the hydroxyapatite (eHA and sHA) determined by variety analysis, e.g. XRD pattern, infrared spectrum FT-IR, SEM (scanning electron microscope) analysis, inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-OES)(See page 114,116, Figures 1-4). Lee teaches elemental analysis of hydroxyapatite made from egg or seashell contain other minerals, e.g. Mg, Na, K, Si, etc. which reads on instantly claimed minerals (See Table 2, page 117). For example, Lee teaches Mg in hydroxyapatite made from eggshell is 3472 ppm which falls within the range of from 500 to 20000 ppm by mass.
Regarding claim 13, Lee teaches K is 524 ppm. As disclosed by instant spec (See page 6, line 24 ), the content of each of Na , K and Si is not particularly limited.
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Regarding the size of hydroxyapatite crystalline, Lee teaches egg hydroxyapatite is approximately 0.8 μm x 0.5 μm, determined by X-ray analysis based on diffraction peak (See Figure 3). Lee is silent about the “crystallite size of 50 to 120 Å” . However, instant hydroxyapatite is a mixture of fine crystallized hydroxyapatite or a mixture low crystalline hydroxyapatite. Lee’s microcrystalline is considered as reading on the mixture of low crystalline hydroxyapatite.
Lee teaches animal study where both hydroxyapatite (eHA and sHA) showed bone regeneration ability(See page 115, page 118). Lee teaches the advantages of using shells as biological material for bone graft materials as cost-effective and safe compared with other commercial product (See page 113). Lee teaches Mg enriched HA and Mg-calcium-phosphate cement show favorable results in bone regeneration in vivo and in vitro, and the higher concentrations of Mg in egg HA might be related to the greater bone regeneration(See page 119, right column).
Lee is silent about the specific formula as recited in instant claim 12. Lee prepared the hydroxyapatite from the same biological material (CaO from eggshell) following similar process as instant application: “the recycled seashells and eggshells were collected and washed with detergent, then calcinated in air at 900°C for 3 h. Calcinated shells were crushed and milled by a ball mill (Fritsch, GmBH) with alumina balls and bowls. The crushed seashells or eggshells were reacted with phosphoric acid in an exothermic reaction. These mixtures were milled for 3 h (eggshells) and 10 h (sea'>hells) at 350 rpm to achieve a homogeneous mixture” (See method of hydroxyapatite preparation, page 114; Table 1). The hydrothermal synthesis process taught by Lee is similar process as disclosed in instant specification (page 7): “The method for producing the hydroxyapatite of the present invention is not particularly limited. As an illustrative example, the aforementioned biologically derived material is subjected to firing to yield calcium oxide, and the resultant calcium oxide is suspended in water or alcohol. To the resultant suspension is added a solution of phosphoric acid in water or alcohol, or alternatively, to the solution of phosphoric acid in water or an alcohol is added the suspension of the calcium oxide in water or alcohol, to thereby obtain a hydroxyapatite slurry”. As such, it is reasonably believed that Lee’s hydroxyapatite product made from the same biological material (CaO from eggshell) following similar process would be similar as instantly claimed hydroxyapatite.
In the alternative, even if the claimed hydroxyapatite is not identical to the hydroxyapatite taught by the cited reference with regard to some unidentified characteristics, the differences between what is disclosed and what is claimed are considered to be so slight that hydroxyapatite taught by the cited reference is likely to possess the similar characteristics/properties of the claimed hydroxyapatite. Thus, instant claimed hydroxyapatite would have been obvious to those of ordinary skill in the art within the meaning of 35 USC 103. As stated in MPEP 2144.05 I, “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 re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976)” Similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. MPEP 2144.05. It would have been obvious to one of the ordinary skill in the art to explore/optimize conditions based on the teachings of Lee, together with routine experimentation and optimization based on general knowledge of crystallization and preparation of hydroxyapatite and arrived at instantly claimed invention. Accordingly, the claimed invention as a whole was at least prima facie obvious, if not anticipated by the cited reference, especially in the absence of sufficient, clear, and convincing evidence to the contrary.
With respect to the USC 102/103 rejection above, please note that the Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether Applicant’s claimed hydroxyapatite is different and, if so, to what extent, from that of the discussed reference.
Response to Arguments
Applicant argues “Lee does not teach or suggest hydroxyapatite as presently claimed...” and further argues about the crystallite size and synthesis temperature, “Lee is approximately 0.8 pm x 0.5 pm, which is clearly larger than that of the hydroxyapatite of the present application. This difference between the crystallite size of the hydroxyapatite of the present claims and that of the hydroxyapatite disclosed in Lee is due to differences in the production methods thereof. Specifically, in the present invention, hydroxyapatite particles are obtained by evaporating a hydroxyapatite slurry. In contrast, in Lee's method, milled hydroxyapatite powders are sintered at 900°C for 2 hours in air” (Remarks, page 6/7).
RESPONSE: Applicant’s arguments are fully considered, but not persuasive. Lee teaches the same raw material from eggshell and similar synthesis process as instantly disclosed Example 1. The heating temperature range disclosed by instant specification is considered as experimentation and optimization based on prior art and general knowledge of hydroxyapatite. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. MPEP 2144.05. Thus, the claimed hydroxyapatite would have been obvious to those of ordinary skilled in the art within the meaning of 35 USC 103. Please note instant claims are hydroxyapatite product, wherein the production process/steps, source of material, etc. do not necessarily add patentability weight to the product.
Claims 1, 12 and 13 are rejected under 35 U.S.C. 102(a)(1) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Nakamura et al. (JP 2016147799 A, Applicant’s IDS dated 10/26/2020, Citation No. 14, machine translated copy powered by EPO and Google), as evidenced by Lee et al. (Tissue Engineering and Regenerative Medicine, Vol. 11, No. 2, 2014, pages 113-120, Applicant’s IDS dated 12/08/2023, “Comparative Study of Hydroxyapatite Prepared from Seashells and Eggshells as a Bone Graft Material”).
Nakamura teaches low-crystalline hydroxyapatite having a crystallite size of 10 to 200 Å made from calcium oxide (CaO) from biological source as the starting material (See abstract , [0007] MT translated Description). Nakamura teaches the calcium oxide can be obtained by burning the shell, scales and/or bones of an organism, e.g. shells of scallops, oyster and the like (See translated Description [0016]). Nakamura teaches the calcium oxide powder can be prepared by calcining the shell, scales and/or bones of an organism, at a temperature of 800-1050° C. for 1-12 hours, pulverized before or after baking,(See [0016] of MT translated Description). Nakamura teaches the low-crystalline hydroxyapatite made from biological material can be easily and efficiently adhered to a base material suitable for mass production (See [0007]-[0008], MT translated Description).
Regarding the crystallite size limitation of hydroxyapatite , Nakamura teaches the hydroxyapatite having a crystallite size of 10 to 200 Å, preferably 30 to 150 Å at the peak appearing at 2θ of 31.500 to 32.500°, as shown in X-ray analysis of low-crystalline hydroxyapatite (See MT translated Description[0010], [0019]). Nakamura teaches evaporating process wherein substrate may be heated during and/or after evaporating the solvent in order to achieve good production efficiency and promote low crystallization of apatite wherein the heating temperature is preferably 40 to 300°C, more preferably 40 to 180°C, even more preferably 80 to 150°C (See [0022]).
Nakamura does not explicitly teach hydroxyapatite made from shells comprise Mg and other mineral or has specific molecular atoms/ratio as recited in claim 12. However, Nakamura teaches additives may be added to the hydroxyapatite dispersion for the purpose of improving the performance and modifying the properties of the low-crystalline(See [0019]). Nakamura teaches hydroxyapatite was prepared from the same biologically derived material (CaO from shell) following similar process as instant application: burning shells as a raw material, pulverizing the powder, and adding calcium oxide (CaO) powder to a phosphoric acid solution gradually under strong stirring conditions(See [0016]). It is reasonably believed that the low-crystalline hydroxyapatite product made by Nakamura would be the same or only slightly different than instant claimed hydroxyapatite comprising Mg and other mineral such as Na, K and Si.
Further, as evidenced by Lee which teaches hydroxyapatite prepared from seashells and eggshells as bone graft material, Lee teaches shells (egg or seashell) contain other minerals, e.g. Mg, Na, K, Si, etc. which reads on instantly claimed other minerals(See Table 2, page 117).
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In the alternative, even if the claimed hydroxyapatite is not identical to the hydroxyapatite taught by the cited reference with regard to some unidentified characteristics, the differences between what is disclosed and what is claimed are considered to be so slight that hydroxyapatite taught by the cited reference is likely to possess the same characteristics (including the instantly claimed properties) of the claimed hydroxyapatite. Thus, the claimed hydroxyapatite would have been obvious to those of ordinary skill in the art within the meaning of 35 USC 103. Accordingly, the claimed invention as a whole was at least prima facie obvious, if not anticipated by the cited reference, especially in the absence of sufficient, clear, and convincing evidence to the contrary.
With respect to the USC 102/103 rejection above, please note that the Patent and Trademark Office is not equipped to conduct experimentation in order to determine whether Applicant’s claimed hydroxyapatite is different and, if so, to what extent, from that of the discussed reference.
Response to Arguments
Applicant argues Nakamura does not teach or suggests, hydroxyapatite as claimed in claim 1, comprising Mg, Na, K, and Si, wherein the hydroxyapatite is derived from eggshell… The raw material for Nakamura's hydroxyapatite is either a reagent or scallop shells, both of differ from the eggshell raw material of the present invention... Hydroxyapatite derived from scallop shells contains less than 500 ppm by mass of Mg and less than 10 ppm by mass of K. In contrast, the hydroxyapatite of the present invention has a content of Mg in a range of from 500 to 20,000 ppm by mass, which is much higher than the Mg content in Nakamura's hydroxyapatite”.
RESPONSE: Nakamura teaches the calcium oxide can be obtained by burning the shell, scales and/or bones of an organism, e.g. shells of scallops, and the like. Although Nakamura is silent about the component of eggshell comprising Mg, Na, K, Si, etc. the shell taught by Nakamura is considered as encompassing eggshell as instantly claimed. Further, Lee teaches shells (egg or seashell) contain other minerals, e.g. Mg, Na, K, Si, etc. which reads on instantly claimed other minerals. A skilled artisan would have known when the calcium salt comprising Mg, Na, K, Si from egg shells as taught by Lee is incorporated into the microcrystalline hydroxyapatite prepared by Nakamura, the resulting hydroxyapatite would contain Mg, Na, K, Si from the eggshell source. As such, the claimed invention as a whole was at least prima facie obvious, especially in the absence of sufficient, clear, and convincing evidence to the contrary.
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 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.
Claims 1, 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Nakamura et al. (JP 2016147799 A, Applicant’s IDS dated 10/26/2020, Citation No. 14, machine translated copy powered by EPO and Google), in view of Lee et al. (Tissue Engineering and Regenerative Medicine, Vol. 11, No. 2, 2014, pages 113-120, Applicant’s IDS dated 12/08/2023, “Comparative Study of Hydroxyapatite Prepared from Seashells and Eggshells as a Bone Graft Material”)(as necessitated by amendment) .
The collective teachings of Nakamura and Lee are elaborated in preceding 102/103 rejection and applied as before. Nakamura teaches microcrystalline hydroxyapatite made from biological material (e.g. shells) having a crystallite size of 10 to 200 Å, preferably 30 to 150 Å. Lee teaches hydroxyapatite made from biological material (e.g. shells) comprise Mg, Na, K, Si.
It would have been obvious to one of the ordinary skill in the art before the effective filing date of instant application to further explore hydroxyapatite made from shell based on the combined teachings of Nakamura and Lee because both teachings are directed to microcrystalline hydroxyapatite made from shell. Nakamura teaches the low-crystalline hydroxyapatite made from biological material can be easily and efficiently adhered to a base material suitable for mass production. Lee teaches the advantages of using shells as biological material for bone graft materials as cost-effective and safe compared with other commercial product. A skilled artisan would be motivated to further explore hydroxyapatite made from shell (e.g. eggshell) based on the beneficial teachings of Nakamura and Lee. The combined teachings of Nakamura and Lee would provide microcrystalline hydroxyapatite comprising multiple minerals with desired chemical compositions and crystalline size that can be easily efficiently adhered to a base material suitable for mass production.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art, together with further experimentation/optimization based on general knowledge of hydroxyapatite. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 1, 12 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Riman et al. (US 2002/0127260, Applicant’s IDS dated 10/26/2020) in view of Nakamura et al. (JP 2016147799 A, Applicant’s IDS dated 10/26/2020, Citation No. 14, machine translated copy powered by EPO and Google) and Lee et al. (Tissue Engineering and Regenerative Medicine, Vol. 11, No. 2, 2014, pages 113-120, Applicant’s IDS dated 12/08/2023, “Comparative Study of Hydroxyapatite Prepared from Seashells and Eggshells as a Bone Graft Material”).
Riman discloses a stable magnesium-substituted crystalline hydroxyapatite containing from about 2.0 to about 29 wt % magnesium (abstract, Examples 1-2, claims 1-5). Riman teaches embodiments comprising crystal having a particle size between about 5 nm and about 100 microns ([0013], [0037], claim 5) (which is considered as mixture of finely crystallized hydroxyapatite or low crystalline hydroxyapatite .
Regarding the chemical formula of claim 12, Riman explicitly teaches magnesium-substituted crystalline hydroxyapatite having the chemical formula
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with X/10 representing atom-percent substitution of magnesium ions for calcium ions ([0003]-[0004]). Riman further teaches magnesium-substituted crystalline hydroxyapatite examples having chemical formula
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and
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(Example 1, Example 2, [0041], [0047]) that read on the limitation of “(Ca:Mg)10 (PO4)(OH)2 wherein Ca atoms and Mg atoms equals to 10 with the number of Ca atoms being from 7 to 9, and the number of Mg atoms being from 1 to 3”.
Riman is silent about the hydroxyapatite is derived from eggshell. However, the limitation “derived from eggshell” drawing to the source of the product rather than a product feature per se does not necessarily contribute to the structural limitation of hydroxyapatite product.
The collective teachings of Nakamura and Lee are elaborated in preceding 102/103 rejection and applied as before. Nakamura teaches microcrystalline hydroxyapatite made from biological material (e.g. shells) having a crystallite size of 10 to 200 Å, preferably 30 to 150 Å. Lee teaches hydroxyapatite made from biological material (e.g. shells) comprise Mg, Na, K, Si.
It would have been obvious to one of the ordinary skill in the art before the effective filing date of instant application to incorporate the calcium salt from biological material (e.g. egg shells) taught by Nakamura and Lee into the microcrystalline hydroxyapatite comprising multiple minerals taught by Riman together with further experimentation/optimization based on general knowledge of hydroxyapatite, and arrive at the instant invention with reasonable expectation of success. At the time the invention was made, it was known that microcrystalline hydroxyapatite comprising Mg could be made as taught by Riman. It’s was also known that calcium salt from biological material (e.g. shells) are used to make microcrystalline hydroxyapatite as taught by Nakamura and Lee. Lee further teaches hydroxyapatite made from biological material (e.g. shells) comprise Mg, Na, K, Si.
The skilled artisan would be motivated to combine the teachings of Riman, Nakamura and Lee because all teachings are directed to microcrystalline hydroxyapatite, Nakamura teaches the low-crystalline hydroxyapatite made from biological material can be easily and efficiently adhered to a base material suitable for mass production. Lee teaches the advantages of using shells as biological material for bone graft materials as cost-effective and safe compared with other commercial product. The combined teachings of Riman, Nakamura and Lee would provide microcrystalline hydroxyapatite comprising multiple minerals with desired chemical compositions and crystalline size that can be easily and efficiently adhered to a base material suitable for mass production at low cost.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art, together with further experimentation/optimization based on general knowledge of hydroxyapatite. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Claim 1, and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Landi et al. (US 2008/0262121, Applicant’s IDS dated 10/26/2020, under “US Patent Documents”, Citation No. 3), in view of Nakamura et al. (JP 2016147799 A, Applicant’s IDS dated 10/26/2020, Citation No. 14, machine translated copy powered by EPO and Google) and Lee et al. (Tissue Engineering and Regenerative Medicine, Vol. 11, No. 2, 2014, pages 113-120, Applicant’s IDS dated 12/08/2023, “Comparative Study of Hydroxyapatite Prepared from Seashells and Eggshells as a Bone Graft Material”)
Regarding hydroxyapatite comprising multi minerals, Landi teaches a hydroxyapatite multi-substituted with physiologically compatible ion species (e. g. magnesium, sodium, Si) and its biohybrid composite with a natural and/or synthetic polymer, which are useful in the preparation of a biomimetic bone substitute (abstract, [0007], [0009], [0012], [0019], Table II, Table III, Example 1, claims 26 and 31-33).
Landi teaches chemical compositions of hydroxyapatite comprising Ca, Mg and/or Si, e.g. SiMgHA; MgHA; SrMgHA (Table II and Table III, [0074]) and multi-substituted non-stoichiometric hydroxyapatite represented by chemical formula ([0096])
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.
Landi teaches chemical compositions of hydroxyapatite wherein Mg2+ is present in a molar ratio of Mg2+ to Ca2+ of hydroxyapatite of 0.01 to 0.30, corresponding to a percent molar ratio Mg/Ca of 1.00% to 30%([0041], claim 31). For hydroxyapatite comprising Mg wherein W=0, X=0, Y=0, z=2, molar ratio Mg/Ca =0.25, the formula of Ca8Mg2(PO4)6(OH)2 would read on the limitation of instant claim 12.
Regarding the crystallite size, Landi teaches TEM (Transmission Electron Microscopy) and XRD (X-Ray Diffraction) analysis of hydroxyapatite embodiments comprising small crystallites size and explicitly teaches multi-substituted hydroxyapatites have a size of 20 nm to 40 nm and nucleuses having a size of 5 nm to 10 nm ([0027]-[0028]; Figures 2-4)(which reads on instantly claimed crystalline size of 50 to 120 Å, i.e. 5nm to 12 nm).
The collective teachings of Nakamura and Lee are elaborated in preceding 102/103 rejection and applied as before. Nakamura teaches microcrystalline hydroxyapatite made from biological material (e.g. shells) having a crystallite size of 10 to 200 Å, preferably 30 to 150 Å. Lee teaches hydroxyapatite made from biological material (e.g. shells) comprise Mg, Na, K, Si.
It would have been obvious to one of the ordinary skill in the art before the effective filing date of instant application to incorporate the calcium salt from biological material (e.g. shells) taught by Nakamura and Lee into the microcrystalline hydroxyapatite comprising multiple minerals (e.g. Mg, Si, Na ) taught by Landi, together with further experimentation/optimization based on general knowledge of hydroxyapatite, and arrive at the instant invention with reasonable expectation of success. At the time the invention was made, it was known that microcrystalline hydroxyapatite comprising multiple minerals (Mg, Na, Si, etc.) could be made as taught by Landi. It’s was also known that calcium salt from biological material (e.g. shells) are used to make microcrystalline hydroxyapatite as taught by Nakamura and Lee. Lee further teaches hydroxyapatite made from biological material (e.g. shells) comprise Mg, Na, K, Si.
The skilled artisan would be motivated to combine the teachings of Landi ,Nakamura and Lee because all teachings are directed to microcrystalline hydroxyapatite, Nakamura teaches the low-crystalline hydroxyapatite made from biological material can be easily and efficiently adhered to a base material suitable for mass production. Lee teaches the advantages of using shells as biological material for bone graft materials as cost-effective and safe compared with other commercial product. The combined teachings of Landi, Nakamura and Lee would provide microcrystalline hydroxyapatite comprising multiple minerals with desired chemical compositions and crystalline size that can be easily and efficiently adhered to a base material suitable for mass production at low cost.
One of ordinary skill in the art would have had reasonable expectation of success in producing the claimed invention based on the combined teachings of prior art, together with further experimentation/optimization based on general knowledge of hydroxyapatite. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant argues “Landi does not teach or suggest hydroxyapatite as claimed in claim 1, comprising Mg, Na, K, and Si. Specifically, Landi does not disclose a composition of hydroxyapatite containing Na and/or K”.
RESPONSE: Please note new claim 12 is independent claim that does not depend on claim 1 and does not require the presence of Na or K in the hydroxyapatite. Landi teaches hydroxyapatite comprising Ca, Mg and/or Si that read on instantly claimed hydroxyapatite comprising multiple component. Further, Lee teaches hydroxyapatite prepared from eggshells contain other minerals, e.g. Mg, Na, K, Si, etc. When the calcium salt comprising Mg, Na, K, Si from shells taught by Nakamura and Lee are incorporated into the microcrystalline hydroxyapatite prepared as taught by Landi, the resulting microcrystalline hydroxyapatite would contain Mg, Na, K, Si from the eggshell source. Therefore, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Please note the limitation " wherein the hydroxyapatite is derived from eggshell " is directed to the source of the product rather than a product feature per se and does not define the structure, properties of the claimed hydroxyapatite product. The product source does not matter as long as the product itself is the same as that would be made from biologically material, especially in the absence of sufficient, clear, and convincing evidence to the contrary.
Conclusion
No claims are allowed.
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/L.M./ Examiner, Art Unit 1628
/JARED BARSKY/Primary Examiner, Art Unit 1628
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