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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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 1-2, 5, 8-12, 24, and 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over Berg et al. (ACS Biomater. Sci. Eng. 2020, 6, 3599−3607) in view of Engqvist et al. (US 2012/0134919 A1).
Regarding claim 1, Berg teaches hollow calcium phosphate particles (calcium magnesium phosphate) having a mean diameter of 310 nm (p. S2, ¶ 1) wherein the hollow calcium phosphate nanoparticles comprise a respective shell comprising calcium, phosphate, water, and magnesium (p. 3600, col. 2, ¶ 1).
Berg further teaches the calcium:phosphate weight ratio being 22:58, which correspond to a Ca:P atomic ratio of 0.9 (0.55 mol Ca2+ to 0.61 mol PO43-), the magnesium (Mg2+) content being 6% by weight, the calcium (Ca2+) content being 22% by weight (p. 3600, col. 2, ¶ 1), and that the particles are amorphous (title), which has the same definition in the art as that provided in the specification for X-ray amorphous: “a material or particles that lacks or lack long range crystal order” (p. 9, lines 23-24). Berg does not teach the particles containing strontium or having a mean diameter within the instantly claimed range.
However, Engqvist teaches similar spherical, hollow calcium phosphate particles and further teaches that the diameter of the particles may be controlled by adjusting the substituted ions in the growth solution, and that the diameter is preferably in the range of 10 nm-1.0 μm, or more than 100 nm and less than 1.0 μm, both of which overlap with the instantly claimed range of 400 nm to 1.5 μm. Engqvist also teaches that strontium is chemically and physically closely related to calcium, that it is easily introduced as a natural substitution for calcium in calcium phosphate, and that strontium has proved to have the effects of increasing bone formation and reducing bone resorption, leading to a gain in bone mass and improved bone mechanical properties in normal animals and humans, increased material properties in hydroxyapatite ([0006]), and that it has beneficial effects against hypersensitivity in teeth ([0191]). Engqvist further teaches that strontium can be incorporated at levels of less 10% ([0053]), which overlaps with the instantly claimed Sr2+ content of 1-6 wt-%.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the particles of Berg by incorporating strontium at levels of less than 10 wt% and to have sizes from 100 nm to 1.0 μm, as taught by Engqvist. One of ordinary skill in the art would have been motivated to incorporate strontium because Engqvist teaches that strontium increases bone mass and strengthens hydroxyapatite ([0006]). One would have been further motivated to modify the sizes into the claimed ranges because Engqvist teaches that the ion substitutions being performed to introduce the strontium will affect the size of the particles and that a preferable particle size is in the range of 100 nm to 1.0 μm.
It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
The courts have also found that “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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II. Accordingly, the claimed ranges of diameters and strontium content merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Regarding claim 2, modified Berg teaches the particles of claim 1, and because the particles are hollow, the composition of the particles will be the composition of the shells, and therefore also meet the limitations of the instant claim.
Regarding claim 5, modified Berg teaches the particles of claim 1, where Engqvist teaches strontium-containing particles having shell thicknesses of approximately 100 nm ([0148]), which lies in the instantly claimed range.
Regarding claim 8, modified Berg teaches the particles of claim 1, where both Berg (p. 3600, col. 2, ¶ 1) and Engqvist (abstract and [0043]) teach the particles being substantially spherical.
Regarding claim 9, modified Berg teaches the particles of claim 1, where Berg teaches that the particles contain water after drying (p. 3600, col. 2, ¶ 1), from which one can conclude that the remaining water is bound water.
Regarding claims 10-12 , modified Berg teaches the particles of claim 1, and Engqvist teaches that their ion-substituted calcium phosphate particles can be mixed with glycerol, a paste-forming compound, in order to provide compositions for tooth repair and regeneration ([0065]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the particles of modified Berg into a composition with glycerol, thereby arriving at the instantly claimed invention of claims 10-12. One of ordinary skill in the art would have been motivated to do so in order to provide a means of delivering the particles for treatment in tooth repair and regeneration, as taught by Engqvist ([0065]).
Regarding claims 24 and 29, modified Berg teaches the particles of claim 1, and Engqvist teaches that their ion-substituted calcium phosphate particles can be incorporated into toothpaste ([0074]).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the particles of modified Berg into toothpaste. One of ordinary skill in the art would have been motivated to do so because Engqvist suggests this as one application of very similar particles.
Because a toothpaste product is a paste, it would also necessarily contain a paste-forming compound, and therefore the combination of Berg and Bergqvist also make obvious the limitations of claim 29.
Regarding claim 30, modified Berg teaches the particles of claim 1. The stability of said particles is expected to be a function of their composition and structure. Because the particles of modified Berg would be substantially identical in composition and structure to the particles instantly disclosed, it is expected that that particles would have similar stability, and therefore meet the limitations of the instant claim.
"Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Furthermore, the instant claim is very broad as to the conditions under which the particles must be stable. Engqvist teaches that their similar amorphous particles are stable in solution at room temperature for at least 13 days ([0175]-[0176]), while the particles of Berg undergo slow crystallization after 24 hours in solution at the elevated temperature of 37 °C (amorphous structure kept for samples with immersion times up to 24 h; p. 3602, Phase Composition and Fig. 3). Storage under very low temperature conditions, for example at -80 °C, would therefore be expected to extend the stability of the particles suggested by the combination of Berg and Engqvist for at least a month.
Once a reference teaching product appearing to be substantially identical is made the basis of a rejection, and the examiner presents evidence or reasoning to show inherency, the burden of production shifts to the applicant. "[T]he PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of [their] claimed product. Whether the rejection is based on inherency’ under 35 U.S.C. 102, on prima facie obviousness’ under 35 U.S.C. 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO’s inability to manufacture products or to obtain and compare prior art products." In re Best, 562 F.2d 1252, 1255, 195 USPQ 4380, 483-34 (CCPA 1977)), see MPEP 2112.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Berg et al. (ACS Biomater. Sci. Eng. 2020, 6, 3599−3607) in view of Engqvist et al. (US 2012/0134919 A1), as applied to claim 1, and further in view of Xia et al. (ACS Biomater. Sci. Eng. 2016, 2, 734−740).
Regarding claim 4, modified Berg teaches the particles of claim 1, where Engqvist teaches the particles can have diameters in the range of 100 nm to 1.0 μm, and further teaches that the particle morphology can be controlled with strontium ion concentration, calcium-to-phosphate ratios, temperature, and heat treatment ([0150], [0152], and [0156]). However, neither Berg nor Engqvist specifically teach particles having mean diameters in the range of from 700 nm to 1.5 μm.
However, Xia also teaches strontium substituted calcium phosphate hollow spheres in dental treatments (abstract), and further teaches that particle size is an important feature of their effectiveness (a proper size of particles, submicrometer with less aggregation, will help the penetration into tubules; p. 734, col. 2, ¶ 1; when choosing a bioactive material for dental tubules occlusion, the size and morphology are important; p. 737, col. 1, ¶ 1). The size of the particles used by Xia was 685 nm, which is smaller than the size of the tubules (p. 737, col. 1, ¶ 2), which are from 2 to 5.5 μm (p. 736, col. 1, ¶ 3).
While the particles taught by Xia are just outside the range of the instant claim, it is noted the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01). Because the claimed sizes and the 685 nm particles of Xia are both expected to fit within the dental tubules they are expected to have similar properties.
The courts have also found that “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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Claims 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Berg et al. (ACS Biomater. Sci. Eng. 2020, 6, 3599−3607) in view of Engqvist et al. (US 2012/0134919 A1), as applied to claims 1 and 5, and further in view of Weber et al. (US 2009/0319032 A1).
Regarding claims 6 and 7, modified Berg teaches the particles of claim 5. Engqvist further teaches that the particle morphology can be controlled with strontium ion concentration, calcium-to-phosphate ratios, temperature, and heat treatment ([0150], [0152], and [0156]). However, neither Berg nor Engqvist specifically teach particles having mean thickness of the shells in the range of from 200 nm to 300 nm.
However, Weber teaches that hollow spheres with a thickness of about 1 nm to about 1 μm and made of calcium phosphate ([0023]) can be integrated with a coating on an endoprosthesis (abstract). Weber further teaches that it is advantageous to introduce particles (hollow elements) with different wall thicknesses in order to build a variety of drug release profiles ([0012]). Weber also envisions using these prostheses in bone grafts and other orthopedic prostheses as well as in dental implants ([0048]) where the bone growth stimulating behavior taught by Engqvist would be advantageous.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify this thickness of the particles taught by modified Berg, including into the claimed ranges of from 200 nm to 300 nm and around 250 nm, using the methods of Engqvist to effect particles morphology. One of ordinary skill in the art would have been motivated to do so because Weber teaches that it is advantageous to have access to such particles with different thicknesses because they will have different drug-release profiles.
Additionally, it is noted that the courts have held that, where the only difference between the prior art and the claims was a recitation of relative dimensions of the claimed device and a device having the claimed relative dimensions would not perform differently than the prior art device, the claimed device was not patentably distinct from the prior art device. Gardner v. TEC Syst., Inc., 725 F.2d 1338, 220 USPQ 777 (Fed. Cir. 1984), cert. denied, 469 U.S. 830, 225 USPQ 232 (1984). MPEP 2144.04(IV).
Response to Arguments
Applicant's arguments with respect to claim 1, filed 9 February 2026, have been fully considered but they are not persuasive.
Applicant argues, pages 9-11, that one of ordinary skill in the art would not combine Berg and Engqvist to arrive at the instantly claimed invention because Berg teaches amorphous calcium phosphate while Engqvist teaches that inclusion of strontium would afford crystalline particles. Such a conclusion is not supported by the prior art.
Berg specifically teaches that “[s]tabilization of ACP can also be achieved by introducing ions such as Mg2+, Sn2+,Zn2+, Al3+, and Ga3+. Substitution of Ca2+ inhibits the nucleation of HA and enables ACP to maintain its amorphous character” (p. 3600, ¶ 3). While Sr2+ is not recited in this list, Mg2+ is, and magnesium is a component of the composition taught explicitly by Berg. Therefore, one of ordinary skill would not arrive at the conclusion that substituting in a small portion of Sr2+ would destroy the amorphous character of a composition that has been established as possessing the ability to “maintain its amorphous character.”
Furthermore, the teachings of Engqvist cannot be considered as leading one of ordinary skill in the art to the expectation that the introduction of Sr2+ would necessarily cause amorphous calcium phosphate particle to crystallize. In fact, contrary to Applicant’s assertion that “there is no instance in Engqvist in which the inclusion of strontium …does not result in a crystalline particle”, Engqvist does teach amorphous strontium-containing calcium phosphate particles:
[0180] The particles prepared with the variations of M3 are shown in FIG. 5'. The particles of (a) are fabricated using M3, showing no difference to M3-Sr, i.e. the version with 0.6 mM strontium (FIG. 1c). The particles in (b) from the solution with doubled ion concentrations, i.e. M3-Sr-2x, showed still spherical particles whereas the fivefold concentration, i.e. M3-Sr-5x, produced irregular shaped particles (c). The particles without carbonate (d) produced with M3-Sr-0HCO3- were much smaller (<100 nm). XRD-analysis resulted in random patterns, which means that all particles of M3 are amorphous. One example of XRD-pattern is shown in FIG. 6'. (emphasis added)
Engqvist further teaches that different substitution ion concentrations can have wide range of effects on size, shape, and morphology ([0136]).
Because Engqvist motivates introduction of Sr2+ into the amorphous particles of Berg, as analyzed above, and because there is no specific teaching away from such a modification found withing Berg or Engqvist, the prior rejection is maintained.
Applicant’s arguments regarding the combination with Xia, pages 12-13, are based first on the assertion that Berg and Engqvist do not teach the composition of claim 1. Applicant additionally notes that Xia’s strontium-containing particles are crystalline particles and therefore Xia teaches away from combining with Berg and Engqvist or results in an unsuitable modification. This argument is not persuasive.
Xia is used only to teach a target size of the particles that would provide beneficial properties. The combination of Berg and Engqvist provide the strontium-containing composition, amorphous morphology, and the ability to tune size of the particles. The fact that Xia’s particles themselves may be crystalline does not teach away from the prior combination to yield strontium-containing amorphous particles, and there is no suggestion that changing the size to allow penetration into tubules, the contribution of Xia, would make the particles crystalline. The combination with Xia is therefore appropriate and is maintained.
Applicant’s remaining argument regarding the combination with Weber, pages 13-14, is based solely on the assertion that Berg and Engqvist do not teach the composition of claim 1. The arguments regarding claim 1 not being persuasive, dependent claims 6-7 were analyzed based upon their further limitations and likewise rejected.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Nicholas A Piro whose telephone number is (571)272-6344. The examiner can normally be reached Mon-Fri, 8:00 am-5:00 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sally Merkling can be reached at (571) 272-6297. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/NICHOLAS A. PIRO/Assistant Examiner, Art Unit 1738
/PAUL A WARTALOWICZ/Primary Examiner, Art Unit 1735