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
Status of Claims
The amendments and arguments filed on 04/06/2026 are acknowledged and have been fully considered. Claims 1-28 are now pending. Claim 1 is amended; claims 8-26 are withdrawn; claim 28 is new. Claims 1-7 and 27-28 are subject of this office action.
Objections/Rejections Withdrawn
Rejections and/or objections not reiterated from previous Office Actions are hereby withdrawn.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, and constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 7 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 7 fails to further limit the claim upon which it depends as the composition claim 1 already comprises polydopamine. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 1-7 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over US PGPUB 20160089477 A1 (Valmikinathan, 2016; as submitted on PTO-892 of 02/11/2025) in view of US PGPUB 20170056559 A1 (Kettenberger, 2017; as submitted on PTO-892 of 02/11/2025) and Huang et al. (2018; as submitted on IDS of 11/15/2022).
In regards to claims 1 and 4, Valmikinathan teaches a wound healing foam that is used for porous bone implants (see Valmikinathan, paragraphs 0033-0036). The composition comprises extracellular matrix (ECM) particulate in the range of 10 to 500 microns (see Valmikinathan, paragraphs 0036 and 0053). Further, Valmikinathan uses UBM particulate, specifically MicroMatrix ®, which is listed in the specification as an ECM particle with a particle size of less than 500 micrometers (see instant specification as filed, paragraph 0010). In regards to the limitation of the biomimetic bone graft material comprising a homogeneous mixture, Valmikinathan teaches that the form is a uniform porous foam (i.e., is homogenous) (see Valmikinathan, paragraph 0055).
In regards to claim 3, the composition also comprises calcium phosphate in the form of hydroxyapatite and tricalcium phosphate (see Valmikinathan, paragraphs 0009, 0051-0052, and claim 13).
In regards claims 5-6, the composition comprises growth factors such as vascular endothelial growth factor and fibroblast growth factor.
In regards to claim 27, it is taught that the foamy ECM slurry is neutralized in solution then dehydrated to form a medical device (i.e., the porous bone implant) (see Valmikinathan, paragraphs 0007, 0047; claim 1).
Valmikinathan is silent on the use of pre-formed particles of calcium phosphate with a diameter of 200µm or less and the composition comprising polydopamine.
Kettenberger teaches a composition for treating bone defects and bone regeneration/healing, among other uses including inlay bone grafts (see Kettenberger, abstract; paragraph 0069). The composition comprises a biological polymer as a carrier, which is collagen or hyaluronan (i.e., a glycosaminoglycan) (see Kettenberger, paragraphs 0010-0012). Hyaluronan is also known as a carrier for growth factors such as BMPs (see Kettenberger, paragraph 0012). The composition also comprises solid particles, such as calcium phosphate in the form of tricalcium phosphate, hydroxyapatite, bioactive glass, apatite, monocalcium phosphate, tetracalcium phosphate, octacalcium phosphate, amorphous calcium phosphate and their combinations (see Kettenberger, abstract; paragraphs 0008, 0033, 0058). The particle size of the solid composition is taught to be 50nm to 10mm, more specifically 175nm to 250nm and most preferably have a mean particle size of 200nm. MPEP 2144.05 states that "[i]n the case where the claimed ranges 'overlap or lie inside ranges disclosed by the prior art' a prima facie case of obviousness exists" quoting In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).
In regards to claims 1 and 5-7, Huang teaches a composition for osteogenic stimulation comprising recombinant human bone morphogenetic protein-2 (rhBMP-2) (i.e., a growth factor) and chondroitin sulfate functionalized calcium phosphate cement (see Huang, abstract). Chondroitin sulfate is a glycosaminoglycan (see Huang, abstract). Further, the composition comprises polydopamine (see Huang, abstract; statement of significance; 2.2. Preparation of CS-ADH). It is taught in the instant specification as filed in paragraph 0157 that “The material is then submerged in a solution of dopamine in tris buffer at pH 8.5, which infuses the material with polydopamine.” Huang teaches a similar method of preparing scaffolds coated with polydopamine (see Huang, 2.3. preparation of CPC-PDA). It is also noted that “infused” is not defined by the specification or claims and as such, it is interpreted as having the broadest reasonable interpretation. In this case, even if the method differs slightly from the instant invention, a coating where the scaffold is dissolved in a polydopamine solution and then dried, would be understood as having the polydopamine infused in the material.
In regards to claims 1-7 and 27, it would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teachings of Valmikinathan with Kettenberger and Huang as all three references teach compositions for healing bone injuries using similar compositions. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose .... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). In the instant case, one with ordinary skill in the art would be motivated to use the particle size of the calcium phosphate of Kettenberger as it is taught that the small size and porous nature of calcium phosphate particles in the composition lead to strong adsorption of therapeutic agents at high affinity, as well as slowly releasing the therapeutic agent (see Kettenberger, paragraph 0065). This allows for a targeted delivery of the therapeutic agents in a controlled manner and promotes the natural bone remodeling process in the region (see Kettenberger, paragraphs 0065-0067). It is also taught that the calcium phosphate, i.e., calcium triphosphate or hydroxyapatite, is blended with the ECM (i.e., UBM) to form a foam (i.e., a homogenous composite formed from the two particles) (see Valmikinathan, paragraphs 0047, 0050-0051). Further, one with ordinary skill in the art would be motivated to combine the polydopamine of Huang with the composition of Valmikinathan and Kettenberger as polydopamine is known to help reduce the degradation of calcium phosphate (see Huang, 3.2. Characterization of CPC-PDA) and works well as a platform for the chondroitin sulfate due to its binding stability, mild treatment, and easy functionality (i.e., it helps bonding the glycosaminoglycan to the calcium phosphate) (see Huang, abstract; Discussion). One with ordinary skill in the art would be motivated to combine the teachings Valmikinathan with the polydopamine of Huang and calcium phosphate particles of Kettenberger according to the known method of creating a wound healing foam (see Valmikinathan, paragraphs 0055-0058) to yield predictable results with a reasonable expectation of success. One with ordinary skill in the art would be motivated to combine prior art elements according to known methods to yield predictable results.
Further, in regards to the limitation of the composite being formed from a one-pot ECM hydrogel at room temperature and neutral pH, a product-by-process limitation, it is noted that the patentability of a product does not depend on its method of production. The combination of Valmikinathan with Kettenberger and Huang teach the instantly claimed biomimetic bone graft material. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). "The Patent Office bears a lesser burden of proof in making out a case of prima facie obviousness for product-by- process claims because of their peculiar nature" than when a product is claimed in the conventional fashion. In re Fessmann, 489 F.2d 742, 744, 180 USPQ 324, 326 (CCPA 1974). Once the examiner provides a rationale tending to show that the claimed product appears to be the same or similar to that of the prior art, although produced by a different process, the burden shifts to applicant to come forward with evidence establishing a nonobvious difference between the claimed product and the prior art product. The teachings of Valmikinathan with Kettenberger and Huang teach the composition as instantly claimed, thus the burden shifts to the applicant to come forward with evidence showing that the process of making the composition as instantly claimed produces a materially different product than the composition of Valmikinathan with Kettenberger and Huang.
Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over US PGPUB 20160089477 A1 (Valmikinathan, 2016; as submitted on PTO-892 of 02/11/2025) in view of US PGPUB 20170056559 A1 (Kettenberger, 2017; as submitted on PTO-892 of 02/11/2025) and Huang et al. (2018; as submitted on IDS of 11/15/2022) as applied to claims 1-7 and 27 above, and further in view of WO 2013169399 A1 (Parhami, 2013).
The teachings of Valmikinathan, Kettenberger, and Huang have been described supra.
The teachings of Valmikinathan, Kettenberger, and Huang are silent on the use of one or more oxysterols.
Parhami teaches a composition, Oxy133 which is a synthetic oxysterol (see Parhami, abstract)(also shown in Table 1 of instant specification as filed; paragraph 0067). It is taught that Oxy133 is useful for treating conditions that would benefit from localized stimulation of bone formation, including, e.g, spine fusion, fracture repair, bone regenerative/tissue engineering applications, augmentation of bone density in the jaw for dental implants, osteoporosis or the like (see Parhami, page 5, lines 11-14). Further it is taught that Oxy133 is used in implants, such as bone grafts (see Parhami, paragraph bridging pages 11-12).
In regards to claim 28, it would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teachings of Parhami with Valmikinathan, Kettenberger, and Huang as all these references teach compositions for healing bone injuries. Further, the Oxy133 is known to work in grafts and provides benefit in localized bone formation. It would be within the purview of one with ordinary skill in the art to use Oxy133 in a composition for treating bone injuries such as that described in Valmikinathan, Kettenberger, and Huang. One with ordinary skill in the art would be motivated to combine the Oxy133 of Parhami with the composition of Valmikinathan, Kettenberger, and Huang according to the known method of creating a wound healing foam (see Valmikinathan, paragraphs 0055-0058) to yield predictable results with a reasonable expectation of success. One with ordinary skill in the art would be motivated to combine prior art elements according to known methods to yield predictable results.
Response to Arguments
Applicant's arguments filed 04/06/2026 have been fully considered but they are not persuasive in view of the modified grounds of rejection as necessitated by amendment.
In regards to applicant’s argument that the teachings of Valmikinathan does not teach the incorporation of pre-formed particulate calcium phosphate within a matrix of separate pre-formed ECM particles, it is pointed out that the rejection has been modified as necessitated by amendment to be over Valmikinathan in view of Kettenberger. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Kettenberger teaches the use of calcium phosphate particles and Valmikinathan teaches that calcium phosphate is blended together with ECM particles to form a foam (i.e., the calcium phosphate particles are homogeneously dispersed within the ECM).
Applicant argues that the prior art doesn’t teach a solid, porous, lyophilized material infused with polydopamine and the method of Huang is for surface coating rather than infusing polydopamine, it is pointed out that the teachings of Valmikinathan, Kettenberger, and Huang teach that the calcium phosphate and ECM particles are blended together to form a homogeneous foam, which is understood to be a composite composition of both types of particles. Further, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). In the instant case, it is taught in the instant specification as filed in paragraph 0157 that “The material is then submerged in a solution of dopamine in tris buffer at pH 8.5, which infuses the material with polydopamine.” Huang teaches a similar method of preparing scaffolds coated with polydopamine (see Huang, 2.3. preparation of CPC-PDA). It is also noted that “infused” is not defined by the specification or claims and as such, it is interpreted as having the broadest reasonable interpretation. In this case, even if the method differs slightly from the instant invention, a coating where the scaffold is dissolved in a polydopamine solution and then dried, would be understood as having the polydopamine infused in the material. As such the teachings of the prior art would lead one with ordinary skill in the art to formulate the composition as instantly claimed.
Conclusion
No claims 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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/ISIS A GHALI/Primary Examiner, Art Unit 1611
/A.A.A./Examiner, Art Unit 1611
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