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 . Claims included in the prosecution are claims 8-27 and 35-40.
Applicants' arguments, filed 04/23/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. 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
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.
1. Claims 8-15, 18-27 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Shi et al. (Preparation of a Silicate Substituted Calcium Deficient Hydroxyapatite by Coprecipitation, Feb. 15, 2007) (hereinafter Shi) in view of Gibson et al. (WO 2010/079316, Jul. 15, 2010) (IDS reference) (hereinafter Gibson) and Obadia et al. (Calcium-Deficient Apatite Synthesized by Ammonia Hydrolysis of Dicalcium Phosphate Dihydrate: Influence of Temperature, Time, and Pressure (May 5, 2006) (hereinafter Obadia), as evidenced by Utah Tech (pKa Chart, 2025) and TutorOceanCorp (Frequently Asked Questions about Ammonia (NH3)), 2025).
Shi discloses a coprecipitation method to synthesize silicate-substituted calcium deficient hydroxyapatite (SiCDHA). The starting materials were calcium nitrate tetrahydrate, phosphoric acid, tetraethylorthosilicate, and ammonia water aqueous solution. Calcium nitrate tetrahydrate, phosphoric acid and tetraethylorthosilicate were mixed and stirred for 35 minutes as precursor solution. Ammonia water (i.e., claimed acidic solution) as a precipitator was added to the precursor solution to pH 10. The slurry was aged for 24 hours at 60°C. The precipitate was separated by filtration, washed repeatedly with distilled water, and dried for 24 hours at 105°C. A fraction of dried samples was calcined for 2h at 700°C or 900°C to control their crystallization (page 83, Materials and Methods). The synthesized silicate-substituted calcium deficient hydroxyapatite (SiCDHA) may have a Ca/P molar ratio of 1.66 and a Ca/(P+Si) molar ratio of 1.52 (Table 1). Bioactivity of hydroxyapatite is significantly enhanced by incorporation of silicon in its structure (page 83, Introduction).
Shi differs from the instant claims insofar as not disclosing wherein the precursor is a powder having an apatite phase, a Ca/P molar ratio of from 2.3 to 2.6, a Ca/(P+Si) molar ratio of from 1.56 to 1.66, a silicon atom content from 4 to 6 wt. %, a specific surface area of from 10 to 90 m2/g, a formula according to formula (I) of instant claim 11, and a Dv50 less than 100 µm.
However, Gibson discloses an inorganic silicate-substituted calcium phosphate hydroxyapatite having a Ca/P molar ratio in the range of 2.05 to 2.55 and a Ca/(P+Si) molar ratio less than 1.66. The silicon atom content is in the range of 2.9 to 6 wt. %. The hydroxyapatite may be represented by formula (I): Ca10-Ᵹ(PO4)6-x(SiO4)x(OH)2-x wherein 1.1 ≤ x ≤ 2.0 and Ᵹ represents a Ca deficiency (page 4, lines 25-34). The silicate-substituted hydroxyapatite is used as a powder (page 5, lines 17-19). The specific surface area of the powder is in the range 10 to 90 m2/g (page 7, lines 27-28). The powder has an average particle size in the range 0.05 to 100 µm (page 10, lines 13-14). The silicate-substituted hydroxyapatite particle is substantially phase pure with a single silicate-substituted hydroxyapatite phase (page 8, lines 4-11).
Obadia discloses synthesizing calcium-deficient apatites (CDA) with controlled Ca/P ratios via hydrolysis of dicalcium phosphate dihydrate (DCPD; CaHPO4·2H2O) in aqueous ammonia solution. The use of ammonia allows to obtain CDA free of cationic substitution (page 32, right column, first paragraph).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. Shi discloses a coprecipitation method to synthesize silicate-substituted calcium deficient hydroxyapatite (SiCDHA) by combining a precursor with an ammonia aqueous solution. Accordingly, it would have been obvious to one of ordinary skill in the art to have used the inorganic silicate-substituted calcium phosphate hydroxyapatite of Gibson as the precursor in Shi’s method since is a known and effective precursor as it is a silicate-substituted hydroxyapatite that is not calcium deficient as taught by Gibson. One of ordinary skill in the art would have had a reasonable expectation of success since Obadia discloses wherein apatite compounds can become calcium deficient when combined with an aqueous ammonia solution.
In regards to instant claim 8 reciting an acidic solution, Shi discloses an ammonia aqueous solution. As evidenced by TutorOceanCorp, ammonia is a weak acid.
In regards to instant claim 15 reciting wherein the acid component is an acid having a pKa of greater than -1.73, as evidenced by Utah Tech, ammonia has a pKa of 36.
In regards to instant claims 24 and 25 reciting wherein the Ca/P molar ratio is greater than 2.25 to 2.35 or 2.15 to 2.30, Table 1 of Shi discloses wherein the Ca/P molar ratio depends on the amount of Si substitution and Shi discloses in the introduction wherein silicon enhances bioactivity. Therefore, it would have taken no more than the relative skills of one of ordinary skill in the art to have arrived at the claimed Ca/P molar ratio through routine experimentation based on the amount of Si substitution desired for bioactivity enhancement.
In regards to instant claim 18 reciting mixing the acidic solution and the starting material in a weight ratio of at least 5:1, since use of ammonia allows to obtain calcium deficient apatites free of cationic substitution, it would have taken no more than the relative skills of one of ordinary skill in the art to have arrived at the claimed mixing ratio through routine experimentation based on the amount of calcium deficiency desired. 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. See MPEP 2144.05(II)(A).
In regards to instant claim 35 reciting wherein the calcium-deficient silicate-substituted calcium phosphate apatite composition has improved thermal stability as compared to the silicate-substituted calcium phosphate apatite starting material, the instant specification discloses on page 2, lines 30-32 disclose wherein contacting silicate-substituted apatite-like compositions with acidic solutions will prepare derivative materials which exhibit increased thermal stability. As such, since the silicate-substituted calcium deficient hydroxyapatite (SiCDHA) of Shi is contacted with an acidic solution, it exhibits increased thermal stability like the claimed invention.
2. Claims 16 , 17 and 36-40 are rejected under 35 U.S.C. 103 as being unpatentable over Shi et al. (Preparation of a Silicate Substituted Calcium Deficient Hydroxyapatite by Coprecipitation, Feb. 15, 2007) (hereinafter Shi) in view of Gibson et al. (WO 2010/079316, Jul. 15, 2010) (IDS reference) (hereinafter Gibson), Obadia et al. (Calcium-Deficient Apatite Synthesized by Ammonia Hydrolysis of Dicalcium Phosphate Dihydrate: Influence of Temperature, Time, and Pressure (May 5, 2006) (hereinafter Obadia), and further in view of Koroleva et al. (Biomaterial Based on Doped Calcium Carbonate-Phosphate for Active Osteogenesis, Apr. 2012) (hereinafter Koroleva), as evidenced by TutorOceanCorp (Frequently Asked Questions about Ammonium Chloride, 2016) and Common Organic Chemistry (Ammonium Chloride, 2026).
The teachings of Shi, Gibson, and Obadia are discussed above. Shi, Gibson, and Obadia do not teach wherein the ammonia aqueous solution is an aqueous ammonia chloride solution.
However, Koroleva discloses wherein sedimentation of calcium carbonate-phosphate can be carried out in an ammonium chloride environment (page 233, left column, second paragraph).
Generally, it is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use. See MPEP 2144.07. Shi discloses ammonia water as a precipitator. Accordingly, it would have been obvious to one of ordinary skill in the art to have incorporated ammonium chloride as the ammonia source since it is a known and effective precipitator of calcium phosphate compounds as taught by Koroleva.
In regards to instant claims 17 and 38 reciting an ammonium chloride concentration of from 0.01% w/v to 15% w/v and 1% w/v to 15% w/v, respectively, since ammonium chloride is used as a precipitator, it would have taken no more than the relative skills of one of ordinary skill in the art to have arrived at the claimed amount through routine experimentation based on the amount of precipitates desired. 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. See MPEP 2144.05(II)(A).
In regards to instant claims 36 and 39, as evidenced by TutorOceanCorp, ammonium chloride has a pH of 4.5-6.
In regards to instant claim 40, as evidenced by Common Organic Chemistry, ammonium chloride has a pKa of 9.24.
Response to Arguments
Applicant argues that the face that NH3 can sometimes act as an acid does not mean an aqueous ammonia solution (ammonia water) is properly characterized as an acidic solution.
The Examiner does not find Applicant’s argument to be persuasive. As evidenced by TutorOceanCorp above, ammonium chloride is a weak acid. Applicant recites in the claims wherein the acidic solution is an aqueous ammonium chloride solution. Therefore, since a weak acid solution may be used as the claimed acidic solution, the ammonia water of Shi meets the claimed acidic solution. Furthermore, it should be noted that claim 1 does not require a particular pH for the acidic solution. Thus, when interpreted broadly, solution comprising a weak acid meets the limitation of an acidic solution. As such, Applicant’s argument is unpersuasive.
Applicant argues that one skilled in the art would have no reason to select the product of Gibson, an already synthesized silicate-substituted calcium phosphate apatite, and try to use it as one of the precursors in the coprecipitation synthesis method of Shi.
The Examiner does not find Applicant’s argument to be persuasive. As discussed in the rejection, one of ordinary skill in the art would have used the inorganic silicate-substituted calcium phosphate hydroxyapatite of Gibson as the precursor in Shi’s method since is a known and effective precursor as it is a silicate-substituted hydroxyapatite that is not calcium deficient. Applicant has not considered the teachings of Obadia which teaches that apatite compounds can become calcium deficient when combined with an aqueous ammonia solution. Thus, one of ordinary skill in the art would have had a reasonable expectation of success in doing so. As such, Applicant’s argument is unpersuasive.
Applicant argues that contacting the silicate-substituted calcium phosphate apatite of Gibson with ammonia water would not result in a calcium-deficient silicate-substituted calcium phosphate apatite composition with an apatite phase having a Ca/P molar ratio which is lower than the Ca/P ratio of the starting material apatite phase.
The Examiner does not find Applicant’s argument to be persuasive. Mere conclusory statements in the specification, unsupported by objective evidence, are entitled to little weight when the PTO questions the efficacy of those statements. In re Greenfield, 571 F.2d 1185, 197 U.S.P.Q. 227, 229 (C.C.P.A. 1978). As such, Applicant’s argument is unpersuasive since Applicant has not shown with objective evidence that contacting the silicate-substituted calcium phosphate apatite of Gibson with ammonia water would not result in a calcium-deficient silicate-substituted calcium phosphate apatite composition with an apatite phase having a Ca/P molar ratio which is lower than the Ca/P ratio of the starting material apatite phase.
Applicant argues that one skilled in the art would not replace the ammonia water in the process of Shi with an ammonium chloride solution.
The Examiner does not find Applicant’s argument to be persuasive. Although Koroleva discloses a different process, Applicant has not explained why ammonium chloride would not be able to act as an effective precipitator for the method of Shi. As such, Applicant’s argument is unpersuasive.
Applicant argues that an already synthesized silicate-substituted calcium phosphate apatite starting material is contacted with an acidic solution in order to transform that starting material into a calcium-deficient silicate-substituted calcium phosphate apatite composition. This is a transformation reaction from one apatite material into another apatite material. It is not a precipitation reaction.
The Examiner does not find Applicant’s argument to be persuasive. Applicant has not explained why a method of transforming an already synthesized silicate-substituted calcium phosphate apatite starting material to a calcium-deficient silicate-substituted calcium phosphate apatite composition cannot involve a precipitation reaction. As such, Applicant’s argument is unpersuasive.
Conclusion
Claims 8-27 and 35-40 are rejected.
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/TRACY LIU/Primary Examiner, Art Unit 1614
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